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1
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Chen X, Xia Y, Min M, Qin L, Liu Y. Optimal dose of bone marrow mesenchymal stem cell transplantation for experimental ulcerative colitis. Regen Ther 2025; 29:177-183. [PMID: 40225050 PMCID: PMC11986536 DOI: 10.1016/j.reth.2025.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 01/09/2025] [Accepted: 01/19/2025] [Indexed: 04/15/2025] Open
Abstract
Objective To investigate the optimal dose of bone marrow mesenchymal stem cell-transplantation for the ulcerative colitis rat. Methods The BMSC of SD rat were isolated, cultured and labelled with DAPI. SD rats were randomly distributed into 3 groups, Colitis was induced with immune-combined TNBS/ethanol in group A、B、C, 3 groups received caudal vein injection of 1 mL fluids, which contain cell number 1 × 106、5 × 106、1 × 107 separately. 5 rats in each group were sacrificed at day 7 and 14 after injection, Cryostat sections of gut, The number of BMSCs in colon and normal tissue surrounded was observed with fluorescent microscope. Results The DAPI marked BMSCs could been seen in the colic mucosa in each group on day 7、14, more cells in colon than the surrounding normal tissue, compared with 1 × 106 group, More cells in 5 × 106 group (P < 0.05), there were no significant difference (P > 0.05) between 5 × 106 group and 1 × 107 group. There were more cells in colon on 14 day than 7 day, and less in the surrounding normal tissue on 14 day than 7 day. Conclusions The density 5 × 106 is proper of bone mesenchymal stem cells for treatment of ulcerative colitis.
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Affiliation(s)
- Xiaoyun Chen
- Department of Pathology, Wuhan No.1 Hospital, Wuhan, 430030, China
| | - Yan Xia
- School of Biomedical Engineering and Medical Imaging, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, China
| | - Min Min
- School of Clinical Medicine, School of Medicine, Hubei University of Science and Technology, Xianning, 437100, China
| | - Lingzhi Qin
- Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yangsheng Liu
- Department of Neurology, Xianning First People's Hospital, Zhongnan Hospital of Wuhan University, Xianning Hospital, Xianning, 437100, China
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Yu H, Zhang F, He YC, Zhang LS. Quality by design strategy of human mesenchymal stem/stromal cell drug products for the treatment of knee osteoarthritis. World J Stem Cells 2025; 17:106547. [DOI: 10.4252/wjsc.v17.i5.106547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/01/2025] [Accepted: 05/07/2025] [Indexed: 05/26/2025] Open
Abstract
Knee osteoarthritis (KOA), characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder, is one of the leading causes of disability worldwide, which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments. The application of mesenchymal stem/stromal cells (MSCs) as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA. However, the complexity and specificity of the “live” cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization. For instance, despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials, yet significant challenges remain in obtaining regulatory approvals. Thus, there’s an urgent need for the research and development of MSC drugs for KOA. In this review, we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design, including designing the cell production processes, quality control, and clinical applications. In detail, we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters. Collectively, this review aims to meet product performance and robust process design, and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.
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Affiliation(s)
- Hao Yu
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Fan Zhang
- Faculty of Life Sciences and Medicine, Kunming University of Science and Technology, Kunming 650500, Yunnan Province, China
| | - Yi-Chen He
- Department of International, Experimental High School, Beijing Normal University, Beijing 100032, China
| | - Lei-Sheng Zhang
- National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- Shandong Provincial Key Medical and Health Laboratory of Blood Ecology and Biointelligence, The Fourth People’s Hospital of Jinan Affiliated to Shandong Second Medical University, Jinan 250031, Shandong Province, China
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Eom YW, Hong JE, Jung PY, Yoon Y, Yoo SH, Hong J, Rhee KJ, Regmi B, Fatima S, Kim MY, Baik SK, Ryu H, Kwon HY. TGF-β expressed by M2 macrophages promotes wound healing by inhibiting TSG-6 expression by mesenchymal stem cells. PLoS One 2025; 20:e0316692. [PMID: 40257993 PMCID: PMC12011265 DOI: 10.1371/journal.pone.0316692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 03/04/2025] [Indexed: 04/23/2025] Open
Abstract
Wound healing involves the collaboration of multiple cells, including macrophages and fibroblasts, and requires the coordination of cytokines, growth factors, and matrix proteins to regulate the repair response. In this study, we investigated how M2 macrophages regulate expression of the anti-fibrotic and anti-inflammatory regulator tumor necrosis factor-α (TNF-α)-stimulated gene 6 (TSG-6) secreted by adipose tissue-derived stem cells (ASCs) during wound healing. Interleukin (IL)-4/IL-13, which is used to differentiate macrophage M2 phenotypes, increases TSG-6 in ASCs; however, M2 macrophages significantly decrease TSG-6 in ASCs. Transforming growth factor (TGF)-β expression was increased, and TNF-α expression was decreased in M2 macrophages. TGF-β inhibited IL-4/IL-13-induced ASC TSG-6 expression. In addition, TSG-6 suppressed TGF-β-triggered wound closure and fibrogenic responses in LX-2 cells. Collectively, TSG-6 inhibited wound healing, but M2 macrophage-expressed TGF-β prevented TSG-6 production from ASCs, which ultimately helped wound healing. Our results indicate that the balance of TNF-α and TGF-β levels during wound healing regulates TSG-6 production from ASCs, which may ultimately modulate the healing process. Our study findings could contribute to novel therapeutic strategies that manipulate the delicate balance between TNF-α and TGF-β to enhance wound repair and mitigate fibrosis.
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Affiliation(s)
- Young Woo Eom
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Ju-Eun Hong
- Department of Biomedical Laboratory Science, Yonsei University Mirae Campus College of Health Sciences, Wonju, Korea
| | - Pil Young Jung
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Yongdae Yoon
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Sang-Hyeon Yoo
- Department of Biomedical Laboratory Science, Yonsei University Mirae Campus College of Health Sciences, Wonju, Korea
| | - Jiyun Hong
- Department of Biomedical Laboratory Science, Yonsei University Mirae Campus College of Health Sciences, Wonju, Korea
| | - Ki-Jong Rhee
- Department of Biomedical Laboratory Science, Yonsei University Mirae Campus College of Health Sciences, Wonju, Korea
| | - Bhupendra Regmi
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Saher Fatima
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hoon Ryu
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hye Youn Kwon
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
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4
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Chu T, Xiao Z, Xun C, Yang C, Lu M, Wang Y, Chen H, Chen P. Peptidomic profiling of mesenchymal stem cell-derived extracellular vesicles and anti-inflammatory activity of degraded peptides. Int Immunopharmacol 2025; 152:114452. [PMID: 40096816 DOI: 10.1016/j.intimp.2025.114452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/06/2025] [Accepted: 03/07/2025] [Indexed: 03/19/2025]
Abstract
Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are key paracrine mediators involved in various autoimmune diseases. While current research on EVs predominantly focuses on their protein and nucleic acid components, small peptides received less attention. In this study, we found IFN-γ-treated MSC-EVs, as engineered EVs, exhibit better anti-inflammatory effects both in vitro and in vivo. Through LC-MS/MS and bioinformatics analysis, we identified four peptides-C3-1, C3-2, B2M-1, and IFIT3-1-that are highly expressed in IFN-γ-treated MSCs-EVs. These peptides significantly mitigate the proliferation inhibition of HUVEC cells induced by H₂O₂ and enhance their migratory capacity. Furthermore, they downregulate the expression of inflammatory cytokines TNF-α and IL-6 in H₂O₂-induced oxidative stress models of HUVEC and LPS-induced inflammatory models of RAW264.7 macrophages. The peptides also upregulate p-AKT and HIF-1α, with C3-1 demonstrating superior anti-inflammatory efficacy in both cell models. Consistent with the in vitro findings, in vivo experiments revealed that C3-1 reduces LPS-induced inflammatory cell infiltration in liver tissue and restores hepatocyte structural integrity, as evidenced by HE-stained liver sections. Western blot analysis further confirmed that C3-1 upregulates p-AKT expression and suppresses inflammatory cytokines. Collectively, these findings suggest that C3-1 exerts its anti-inflammatory effects via activation of the AKT signaling pathway and regulation of TNF-α and IL-6. This study not only highlights the anti-inflammatory potential of IFN-γ-treated MSC-derived EVs but also identifies C3-1 as a promising candidate for anti-inflammatory drug development. Notably, this is the first study to identify degraded peptides within EVs, providing a foundation for future research in this area.
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Affiliation(s)
- Tianqi Chu
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha 410081, Hunan, China; Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Zixuan Xiao
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
| | - Chengfeng Xun
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China; Hunan Academy of Forestry, Changsha 410081, China
| | - Chunyan Yang
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
| | - Mengqi Lu
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
| | - Yuqiu Wang
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
| | - Haiyan Chen
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha 410081, Hunan, China; East China Institute of Digital Medical Engineering, Shangrao 334000, China.
| | - Ping Chen
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha 410081, Hunan, China; Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China.
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5
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Lee JM, Lee CY, Seol B, Jung CK, Kim Y, Kang D, Yu H, Hong Y, Song CL, Cho YS, Kim M. Tracing genomic instability in induced mesenchymal stromal cell manufacture: an integration-free transfection approach. Exp Mol Med 2025; 57:900-909. [PMID: 40229358 PMCID: PMC12046023 DOI: 10.1038/s12276-025-01439-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 12/06/2024] [Accepted: 02/02/2025] [Indexed: 04/16/2025] Open
Abstract
Here we systematically investigated genomic alterations from the initiation of induced pluripotent stem (iPS) cell generation to induced mesenchymal stromal/stem cell differentiation. We observed a total of ten copy number alterations (CNAs) and five single-nucleotide variations (SNVs) during the phases of reprogramming, differentiation and passaging. We identified a higher frequency of CNAs and SNVs in iPS cells generated using the Sendai virus (SV) method compared with those generated with episomal vectors (Epi). Specifically, all SV-iPS cell lines exhibited CNAs during the reprogramming phase, while only 40% of Epi-iPS cells showed such alterations. Additionally, SNVs were observed exclusively in SV-derived cells during passaging and differentiation, with no SNVs detected in Epi-derived lines. Gene expression analysis revealed upregulation of chromosomal instability-related genes in late-passage SV-iPSCs, further indicating increased genomic instability. Notably, TP53 mutations were identified, underscoring the vulnerability of the gene and the critical need for careful genomic scrutiny when preparing iPS cells and derived cell lines.
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Affiliation(s)
- Jong-Mi Lee
- Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chae Yeon Lee
- Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Medical Sciences, Graduate School of The Catholic University of Korea, Seoul, Republic of Korea
| | - Binna Seol
- Stem Cell Research Laboratory, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Chan Kwon Jung
- Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yonggoo Kim
- Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dain Kang
- Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Haein Yu
- Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yuna Hong
- Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Medical Sciences, Graduate School of The Catholic University of Korea, Seoul, Republic of Korea
| | - Cho Lok Song
- Stem Cell Research Laboratory, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Yee Sook Cho
- Stem Cell Research Laboratory, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
- Department of Bioscience, KRIBB School, University of Science and Technology, Daejeon, Republic of Korea.
| | - Myungshin Kim
- Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
- Department of Medical Sciences, Graduate School of The Catholic University of Korea, Seoul, Republic of Korea.
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6
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Simão VA, Floriano JF, Cesário RC, Tonon KDS, de Oliveira LRC, Delella FK, Almeida F, dos Santos LD, Seiva FRF, de Campos Zuccari DAP, Ribeiro-Paes JT, Reiter RJ, de Almeida Chuffa LG. Extracellular Signaling Molecules from Adipose-Derived Stem Cells and Ovarian Cancer Cells Induce a Hybrid Epithelial-Mesenchymal Phenotype in a Bidirectional Interaction. Cells 2025; 14:374. [PMID: 40072102 PMCID: PMC11899480 DOI: 10.3390/cells14050374] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/24/2025] [Accepted: 02/28/2025] [Indexed: 03/15/2025] Open
Abstract
Ovarian cancer (OC) is characterized by high mortality rates due to late diagnosis, recurrence, and metastasis. Here, we show that extracellular signaling molecules secreted by adipose-derived mesenchymal stem cells (ASCs) and OC cells-either in the conditioned medium (CM) or within small extracellular vesicles (sEVs)-modulate cellular responses and drive OC progression. ASC-derived sEVs and CM secretome promoted OC cell colony formation, invasion, and migration while upregulating tumor-associated signaling pathways, including TGFβ/Smad, p38MAPK/ERK1/2, Wnt/β-catenin, and MMP-9. Additionally, OC-derived sEVs and CM induced a pro-tumorigenic phenotype in ASCs, enhancing their invasiveness and expression of tumor-associated factors. Notably, both ASCs and OC cells exhibited increased expression of E-cadherin and Snail/Slug proteins, key markers of epithelial/mesenchymal hybrid phenotype, enhancing cellular plasticity and metastatic potential. We also demonstrated that these cellular features are, at least in part, due to the presence of tumor-supportive molecules such as TNF-α, Tenascin-C, MMP-2, and SDF-1α in the CM secretome of ASCs and OC cells. In silico analyses linked these molecular changes to poor prognostic outcomes in OC patients. These findings highlight the critical role of sEVs and tumor/stem cell-derived secretome in OC progression through bidirectional interactions that impact cellular behavior and phenotypic transitions. We suggest that targeting EV-mediated communication could improve therapeutic strategies and patient outcomes.
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Affiliation(s)
- Vinícius Augusto Simão
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil
| | - Juliana Ferreira Floriano
- Bioengineering & Biomaterials Group, School of Pharmaceutical Sciences, São Paulo State University (Unesp), Km 01 Araraquara-Jaú Road, Araraquara 14800-903, São Paulo, Brazil
| | - Roberta Carvalho Cesário
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil
| | - Karolina da Silva Tonon
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil
| | - Larissa Ragozo Cardoso de Oliveira
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil
| | - Flávia Karina Delella
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil
| | - Fausto Almeida
- Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo (Usp), Ribeirão Preto 14049-900, São Paulo, Brazil
| | | | - Fábio Rodrigues Ferreira Seiva
- Department of Chemistry and Biochemistry, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil
| | | | - João Tadeu Ribeiro-Paes
- Department of Biotechnology, School of Sciences, Humanities and Languages, São Paulo State University (Unesp), Assis 19806-900, São Paulo, Brazil
| | - Russel J. Reiter
- Department of Cell Systems and Anatomy, UT Health, San Antonio, TX 78229, USA
| | - Luiz Gustavo de Almeida Chuffa
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu 18618-689, São Paulo, Brazil
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Tew VK, Barathan M, Nordin F, Law JX, Ng MH. Emerging Role of Mesenchymal Stromal Cell and Exosome Therapies in Treating Cognitive Impairment. Pharmaceutics 2025; 17:284. [PMID: 40142948 PMCID: PMC11945939 DOI: 10.3390/pharmaceutics17030284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/27/2024] [Accepted: 01/09/2025] [Indexed: 03/28/2025] Open
Abstract
Cognitive aging, characterized by the gradual decline in cognitive functions such as memory, attention, and problem-solving, significantly impacts daily life. This decline is often accelerated by neurodegenerative diseases, particularly Alzheimer's Disease (AD) and Parkinson's Disease (PD). AD is marked by the accumulation of amyloid-beta plaques and tau tangles, whereas PD involves the degeneration of dopaminergic neurons. Both conditions lead to severe cognitive impairment, greatly diminishing the quality of life for affected individuals. Recent advancements in regenerative medicine have highlighted mesenchymal stromal cells (MSCs) and their derived exosomes as promising therapeutic options. MSCs possess regenerative, neuroprotective, and immunomodulatory properties, which can promote neurogenesis, reduce inflammation, and support neuronal health. Exosomes, nanosized vesicles derived from MSCs, provide an efficient means for delivering bioactive molecules across the blood-brain barrier, targeting the underlying pathologies of AD and PD. While these therapies hold great promise, challenges such as variability in MSC sources, optimal dosing, and effective delivery methods need to be addressed for clinical application. The development of robust protocols, along with rigorous clinical trials, is crucial for validating the safety and efficacy of MSC and exosome therapies. Future research should focus on overcoming these barriers, optimizing treatment strategies, and exploring the integration of MSC and exosome therapies with lifestyle interventions. By addressing these challenges, MSC- and exosome-based therapies could offer transformative solutions for improving outcomes and enhancing the quality of life for individuals affected by cognitive aging and neurodegenerative diseases.
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Affiliation(s)
| | | | | | | | - Min Hwei Ng
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia (F.N.); (J.X.L.)
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Nonaka CKV, Costa-Ferro ZSM, Arraes ACP, Weber TL, de Aragão França LS, Silva KN, Souza BSDF. Validation of an automated quality control method to test sterility of two advanced therapy medicinal products: Mesenchymal stromal cells and their extracellular vesicles. Hematol Transfus Cell Ther 2025; 47:103727. [PMID: 39863436 PMCID: PMC12011113 DOI: 10.1016/j.htct.2024.09.2486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 05/22/2024] [Accepted: 09/27/2024] [Indexed: 01/27/2025] Open
Abstract
Mesenchymal stromal cells are multipotent cells present in various tissues that are widely studied for relevant therapeutic potential due to their paracrine immunomodulatory and tissue regenerating properties. Many mesenchymal stromal cell-based products are under investigation for the treatment of different clinical conditions. Recently, the therapeutic potential of the extracellular vesicles released by these cells has been under focus, with emphasis on clinical translation. Sterility testing during manufacture and before the final release of the advanced therapy medicinal products to markets is a critical quality control measure. Therefore, analytical methods for sterility testing in addition to complying with pharmacopeial standards must validate the adequacy of each product and evaluate matrix interference. Here, an automated system for sterility control of reagents used in the bioprocessing of mesenchymal stromal cells and their extracellular vesicles was validated. Reagents (culture media, antibiotics, and excipients in the final product) were inoculated with 10 or 50 colony forming units of microorganisms in BACTEC™ Peds Plus™ T/F aerobic/anaerobic bottles. Under aerobic conditions (BACTEC™ Peds Plus™ T/F aerobic bottles), microbial growth was detected within an acceptable incubation time according to regulatory guidelines. The results of this study corroborate other studies that use automated sterility testing as an alternative to the manual USP<71> compendial method to detect microorganisms close to the limit of detection within an acceptable incubation time.
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Affiliation(s)
| | | | | | | | | | - Katia Nunes Silva
- Hospital São Rafael, Salvador, Bahia, Brazil; Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Bahia, Brazil
| | - Bruno Solano de Freitas Souza
- Hospital São Rafael, Salvador, Bahia, Brazil; Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Bahia, Brazil; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil.
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9
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Zhang L, Deng Y, Bai X, Wei X, Ren Y, Chen S, Deng H. Cell therapy for end-stage liver disease: Current state and clinical challenge. Chin Med J (Engl) 2024; 137:2808-2820. [PMID: 39602326 DOI: 10.1097/cm9.0000000000003332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Indexed: 11/29/2024] Open
Abstract
ABSTRACT Liver disease involves a complex interplay of pathological processes, including inflammation, hepatocyte necrosis, and fibrosis. End-stage liver disease (ESLD), such as liver failure and decompensated cirrhosis, has a high mortality rate, and liver transplantation is the only effective treatment. However, to overcome problems such as the shortage of donor livers and complications related to immunosuppression, there is an urgent need for new treatment strategies that need to be developed for patients with ESLD. For instance, hepatocytes derived from donor livers or stem cells can be engrafted and multiplied in the liver, substituting the host hepatocytes and rebuilding the liver parenchyma. Stem cell therapy, especially mesenchymal stem cell therapy, has been widely proved to restore liver function and alleviate liver injury in patients with severe liver disease, which has contributed to the clinical application of cell therapy. In this review, we discussed the types of cells used to treat ESLD and their therapeutic mechanisms. We also summarized the progress of clinical trials around the world and provided a perspective on cell therapy.
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Affiliation(s)
- Lin Zhang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Kurniawan M, Ramli Y, Putri ND, Harris S, Rasyid A, Mesiano T, Hidayat R. Mesenchymal stem cells therapy for chronic ischemic stroke-a systematic review. ASIAN BIOMED 2024; 18:194-203. [PMID: 39483715 PMCID: PMC11524678 DOI: 10.2478/abm-2024-0027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
Stroke represents a significant global health issue, primarily in the form of ischemic stroke. Despite the availability of therapeutic interventions, the recovery from chronic stroke, occurring 3 months post-initial stroke, poses substantial challenges. A promising avenue for post-acute stroke patients is mesenchymal stem cells (MSCs) therapy, which is derived from various sources and is globally recognized as the most utilized and extensively studied stem cell therapy. This systematic review, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, aims to synthesize evidence regarding the impact of MSCs therapy on patients with chronic ischemic stroke. Employing an advanced search strategy across databases such as PubMed, PubMed Central, Google Scholar, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrial.gov, a total of 70 studies were identified, with 4studies meeting the inclusion criteria. Although positive outcomes were observed in terms of efficacy and safety, certain limitations, such as small sample sizes, study heterogeneity, and the absence of placebo groups, undermine the overall strength of the evidence. It is crucial to address these limitations in future research, highlighting the importance of larger sample sizes, standardized methodologies, and comparative trials to improve the assessment of MSCs' efficacy and safety. Moving forward, key priorities include exploring underlying mechanisms, determining optimal administration modes and dosages, and conducting comparative trials. By addressing these aspects, we can propel MSCs therapies toward greater efficacy, safety, and applicability across diverse patient populations.
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Affiliation(s)
- Mohammad Kurniawan
- Department of Neurology, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
- Stem Cell Medical Technology Integrated Service Unit, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Yetty Ramli
- Department of Neurology, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
- Stem Cell Medical Technology Integrated Service Unit, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Nadira Deanda Putri
- Department of Neurology, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Salim Harris
- Department of Neurology, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Al Rasyid
- Department of Neurology, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Taufik Mesiano
- Department of Neurology, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Rakhmad Hidayat
- Department of Neurology, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
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Starska-Kowarska K. Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer-Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of Stromal Cell-Based Pharmacological Strategies. Cells 2024; 13:1270. [PMID: 39120301 PMCID: PMC11311692 DOI: 10.3390/cells13151270] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 07/11/2024] [Accepted: 07/26/2024] [Indexed: 08/10/2024] Open
Abstract
Head and neck cancer (HNC) entails a heterogenous neoplastic disease that arises from the mucosal epithelium of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being the eighth most common cancer worldwide. It is believed that the mesenchymal/stem stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and patient outcomes; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNC. MSCs are multipotent, heterogeneous and mobile cells. Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties. They may play a key role in the process of acquiring drug resistance and thus in treatment failure. The present narrative review examines the links between MSCs and HNC, as well as the different mechanisms involved in the development of resistance to current chemo-radiotherapies in HNC. It also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy, with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC.
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Affiliation(s)
- Katarzyna Starska-Kowarska
- Department of Physiology, Pathophysiology and Clinical Immunology, Department of Clinical Physiology, Medical University of Lodz, Żeligowskiego 7/9, 90-752 Lodz, Poland; ; Tel.: +48-42-2725237
- Department of Otorhinolaryngology, EnelMed Center Expert, Lodz, Drewnowska 58, 91-001 Lodz, Poland
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Li C, Sun Y, Xu W, Chang F, Wang Y, Ding J. Mesenchymal Stem Cells-Involved Strategies for Rheumatoid Arthritis Therapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2305116. [PMID: 38477559 PMCID: PMC11200100 DOI: 10.1002/advs.202305116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 12/13/2023] [Indexed: 03/14/2024]
Abstract
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints and bone destruction. Because of systemic administration and poor targeting, traditional anti-rheumatic drugs have unsatisfactory treatment efficacy and strong side effects, including myelosuppression, liver or kidney function damage, and malignant tumors. Consequently, mesenchymal stem cells (MSCs)-involved therapy is proposed for RA therapy as a benefit of their immunosuppressive and tissue-repairing effects. This review summarizes the progress of MSCs-involved RA therapy through suppressing inflammation and promoting tissue regeneration and predicts their potential clinical application.
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Affiliation(s)
- Chaoyang Li
- Department of OrthopedicsThe Second Hospital of Jilin University4026 Yatai StreetChangchun130041P. R. China
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of Sciences5625 Renmin StreetChangchun130022P. R. China
| | - Yifu Sun
- Department of OrthopedicsThe Second Hospital of Jilin University4026 Yatai StreetChangchun130041P. R. China
| | - Weiguo Xu
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of Sciences5625 Renmin StreetChangchun130022P. R. China
| | - Fei Chang
- Department of OrthopedicsThe Second Hospital of Jilin University4026 Yatai StreetChangchun130041P. R. China
| | - Yinan Wang
- Department of BiobankDivision of Clinical ResearchThe First Hospital of Jilin University1 Xinmin StreetChangchun130061P. R. China
- Key Laboratory of Organ Regeneration and Transplantation of the Ministry of EducationThe First Hospital of Jilin University1 Xinmin StreetChangchun130061P. R. China
| | - Jianxun Ding
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of Sciences5625 Renmin StreetChangchun130022P. R. China
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Habiba UE, Khan N, Greene DL, Ahmad K, Shamim S, Umer A. Meta-analysis shows that mesenchymal stem cell therapy can be a possible treatment for diabetes. Front Endocrinol (Lausanne) 2024; 15:1380443. [PMID: 38800472 PMCID: PMC11116613 DOI: 10.3389/fendo.2024.1380443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 04/09/2024] [Indexed: 05/29/2024] Open
Abstract
Objective This meta-analysis includes the systematic literature review and meta-analysis involving clinical trials to assess the efficacy and safety of mesenchymal stem cell (MSC) transplantation for treating T1DM and T2DM. Methods We searched PubMed, ScienceDirect, Web of Science, clinicaltrials.gov, and Cochrane Library for "published" research from their inception until November 2023. Two researchers independently reviewed the studies' inclusion and exclusion criteria. Our meta-analysis included 13 studies on MSC treatment for diabetes. Results The MSC-treated group had a significantly lower HbA1c at the last follow-up compared to the baseline (MD: 0.95, 95% CI: 0.33 to 1.57, P-value: 0.003< 0.05), their insulin requirement was significantly lower (MD: 0.19, 95% CI: 0.07 to 0.31, P-value: 0.002< 0.05), the level of FBG with MSC transplantation significantly dropped compared to baseline (MD: 1.78, 95% CI: -1.02 to 4.58, P-value: 0.212), the FPG level of the MSC-treated group was significantly lower (MD: -0.77, 95% CI: -2.36 to 0.81, P-value: 0.339 > 0.05), and the fasting C-peptide level of the MSC-treated group was slightly high (MD: -0.02, 95% CI: -0.07 to 0.02, P-value: 0.231 > 0.05). Conclusion The transplantation of MSCs has been found to positively impact both types of diabetes mellitus without signs of apparent adverse effects.
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Affiliation(s)
- Umm E. Habiba
- Research and Development (R&D) Department, R3 Medical Research LLC, Scottsdale, AZ, United States
- Research and Development (R&D) Department, Pak-American Hospital Pvt. Ltd., Islamabad, Pakistan
- Research and Development (R&D) Department, R3 Stem Cell LLC, Scottsdale, AZ, United States
| | - Nasar Khan
- Research and Development (R&D) Department, R3 Medical Research LLC, Scottsdale, AZ, United States
- Research and Development (R&D) Department, Pak-American Hospital Pvt. Ltd., Islamabad, Pakistan
- Research and Development (R&D) Department, R3 Stem Cell LLC, Scottsdale, AZ, United States
- Research and Development (R&D) Department, Bello Bio Labs and Therapeutics Pvt. Ltd., Islamabad, Pakistan
| | - David Lawrence Greene
- Research and Development (R&D) Department, R3 Medical Research LLC, Scottsdale, AZ, United States
- Research and Development (R&D) Department, Pak-American Hospital Pvt. Ltd., Islamabad, Pakistan
- Research and Development (R&D) Department, R3 Stem Cell LLC, Scottsdale, AZ, United States
- Research and Development (R&D) Department, Bello Bio Labs and Therapeutics Pvt. Ltd., Islamabad, Pakistan
| | - Khalil Ahmad
- Department of Statistics, Quaid-i-Azam University, Islamabad, Pakistan
| | - Sabiha Shamim
- Research and Development (R&D) Department, R3 Medical Research LLC, Scottsdale, AZ, United States
- Research and Development (R&D) Department, Pak-American Hospital Pvt. Ltd., Islamabad, Pakistan
- Research and Development (R&D) Department, R3 Stem Cell LLC, Scottsdale, AZ, United States
| | - Amna Umer
- Research and Development (R&D) Department, R3 Medical Research LLC, Scottsdale, AZ, United States
- Research and Development (R&D) Department, Pak-American Hospital Pvt. Ltd., Islamabad, Pakistan
- Research and Development (R&D) Department, R3 Stem Cell LLC, Scottsdale, AZ, United States
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Wang X, Li F, Wu S, Xing W, Fu J, Wang R, He Y. Research progress on optimization of in vitro isolation, cultivation and preservation methods of dental pulp stem cells for clinical application. Front Bioeng Biotechnol 2024; 12:1305614. [PMID: 38633667 PMCID: PMC11021638 DOI: 10.3389/fbioe.2024.1305614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 03/19/2024] [Indexed: 04/19/2024] Open
Abstract
Due to high proliferative capacity, multipotent differentiation, immunomodulatory abilities, and lack of ethical concerns, dental pulp stem cells (DPSCs) are promising candidates for clinical application. Currently, clinical research on DPSCs is in its early stages. The reason for the failure to obtain clinically effective results may be problems with the production process of DPSCs. Due to the different preparation methods and reagent formulations of DPSCs, cell characteristics may be affected and lead to inconsistent experimental results. Preparation of clinical-grade DPSCs is far from ready. To achieve clinical application, it is essential to transit the manufacturing of stem cells from laboratory grade to clinical grade. This review compares and analyzes experimental data on optimizing the preparation methods of DPSCs from extraction to resuscitation, including research articles, invention patents and clinical trials. The advantages and disadvantages of various methods and potential clinical applications are discussed, and factors that could improve the quality of DPSCs for clinical application are proposed. The aim is to summarize the current manufacture of DPSCs in the establishment of a standardized, reliable, safe, and economic method for future preparation of clinical-grade cell products.
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Affiliation(s)
- Xinxin Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
- First Clinical College of the Ministry of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Fenyao Li
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
- First Clinical College of the Ministry of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Shuting Wu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
- First Clinical College of the Ministry of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Wenbo Xing
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
- First Clinical College of the Ministry of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Jiao Fu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
- First Clinical College of the Ministry of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Ruoxuan Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
- First Clinical College of the Ministry of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Yan He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
- First Clinical College of the Ministry of Medicine, Wuhan University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
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Choi YJ, Kim WR, Kim DH, Kim JH, Yoo JH. Human umbilical cord/placenta mesenchymal stem cell conditioned medium attenuates intestinal fibrosis in vivo and in vitro. Stem Cell Res Ther 2024; 15:69. [PMID: 38454492 PMCID: PMC10921617 DOI: 10.1186/s13287-024-03678-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 02/21/2024] [Indexed: 03/09/2024] Open
Abstract
BACKGROUND A significant unmet need in inflammatory bowel disease is the lack of anti-fibrotic agents targeting intestinal fibrosis. This study aimed to investigate the anti-fibrogenic properties and mechanisms of the conditioned medium (CM) from human umbilical cord/placenta-derived mesenchymal stem cells (UC/PL-MSC-CM) in a murine intestinal fibrosis model and human primary intestinal myofibroblasts (HIMFs). METHODS UC/PL-MSC-CM was concentrated 15-fold using a 3 kDa cut-off filter. C57BL/6 mice aged 7 weeks old were randomly assigned to one of four groups: (1) control, (2) dextran sulfate sodium (DSS), (3) DSS + CM (late-phase treatment), and (4) DSS + CM (early-phase treatment). Chronic DSS colitis and intestinal fibrosis was induced by three cycles of DSS administration. One DSS cycle consisted of 7 days of oral DSS administration (1.75%, 2%, and 2.5% DSS), followed by 14 days of drinking water. UC/PL-MSC-CM was intraperitoneally administered in the late phase (from day 50, 10 times) or early phase (from day 29, 10 times) of DSS cycles. HIMFs were treated with TGF-β1 and co-treated with UC/PL-MSC-CM (10% of culture media) in the cellular model. RESULTS In the animal study, UC/PL-MSC-CM reduced submucosa/muscularis propria thickness and collagen deposition, which improved intestinal fibrosis in chronic DSS colitis. The UC/PL-MSC-CM significantly reduced the expressions of procollagen1A1 and α-smooth muscle actin, which DSS significantly elevated. The anti-fibrogenic effect was more apparent in the UC-MSC-CM or early-phase treatment model. The UC/PL-MSC-CM reduced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs in the cellular model. The UC/PL-MSC-CM downregulated fibrogenesis by suppressing RhoA, MRTF-A, and SRF expression. CONCLUSIONS Human UC/PL-MSC-CM inhibits TGF-β1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and chronic DSS colitis-induced intestinal fibrosis. Thus, it may be regarded as a novel candidate for stem cell-based therapy of intestinal fibrosis.
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Affiliation(s)
- Yoon Jeong Choi
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, South Korea
- Institute of Basic Medical Sciences, CHA University School of Medicine, Seongnam, 13496, South Korea
| | - Woo Ram Kim
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 06273, South Korea
| | - Duk Hwan Kim
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, South Korea
| | - Jee Hyun Kim
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, South Korea.
| | - Jun Hwan Yoo
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, South Korea.
- Institute of Basic Medical Sciences, CHA University School of Medicine, Seongnam, 13496, South Korea.
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Nascimento C, Saraiva MVA, Pereira VM, de Brito DCC, de Aguiar FLN, Alves BG, Roballo KCS, de Figueiredo JR, Ambrósio CE, Rodrigues APR. Addition of synthetic polymer in the freezing solution of mesenchymal stem cells from equine adipose tissue as a future perspective for reducing of DMSO concentration. BRAZILIAN JOURNAL OF VETERINARY MEDICINE 2023; 45:e002523. [PMID: 38162818 PMCID: PMC10756151 DOI: 10.29374/2527-2179.bjvm002523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 12/07/2023] [Indexed: 01/03/2024] Open
Abstract
The regenerative therapies with stem cells (SC) has been increased by the cryopreservation, permitting cell storage for extended periods. However, the permeating cryoprotectant agents (CPAs) such as dimethylsulfoxide (DMSO) can cause severe adverse effects. Therefore, this study evaluated equine mesenchymal stem cells derived from adipose tissue (eAT-MSCs) in fresh (Control) or after slow freezing (SF) in different freezing solutions (FS). The FS comprise DMSO and non-permeating CPAs [Trehalose (T) and the SuperCool X-1000 (X)] in association or not, totalizing seven different FS: (DMSO; T; X; DMSO+T; DMSO+X; T+X, and DMSO+T+X). Before and after cryopreservation were evaluated, viability, colony forming unit (CFU), and cellular differentiation capacity. After freezing-thawing, the viability of the eAT-MSCs reduced (P< 0.05) in all treatments compared to the control. However, the viability of frozen eAT-MSCs in DMSO (80.3 ± 0.6) was superior (P<0.05) to the other FS. Regarding CFU, no difference (P>0.05) was observed between fresh and frozen cells. After freezing-thawing, the eAT-MSCs showed osteogenic, chondrogenic, and adipogenic lineages differentiation potential. Nonetheless, despite the significative reduction in the osteogenic differentiation capacity between fresh and frozen cells, no differences (P > 0.05) were observed among FS. Furthermore, the number of chondrogenic differentiation cells frozen in DMSO+X solution reduced (P<0.05) comparing to the control, without differ (P>0.05) to the other FS. The adipogenic differentiation did not differ (P>0.05) among treatments. In conclusion, although these findings confirm the success of DMSO to cryopreserve eAT-MSCs, the Super Cool X-1000 could be a promise to reduce the DMSO concentration in a FS.
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Affiliation(s)
- Cátia Nascimento
- Veterinarian, MSc. Laboratório de Manipulação de Oócitos e Folículos Pré-Antrais Ovarianos (LAMOFOPA), Faculdade de Medicina Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brazil;
| | | | - Vitoria Mattos Pereira
- Veterinarian, MSc. Departamento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, SP, Brazil;
| | | | | | - Benner Geraldo Alves
- Veterinarian, DSc. Laboratório de Biologia da Reprodução, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil;
| | - Kelly Cristine Santos Roballo
- Veterinarian, DSc. Departamento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, SP, Brazil;
| | - José Ricardo de Figueiredo
- Veterinarian, DSc. LAMOFOPA, Faculdade de Medicina Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brazil;
| | - Carlos Eduardo Ambrósio
- Veterinarian, DSc. Departamento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, SP, Brazil;
| | - Ana Paula Ribeiro Rodrigues
- Veterinarian, DSc. LAMOFOPA, Faculdade de Medicina Veterinária, Universidade Estadual do Ceará, Fortaleza, CE, Brazil.
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Zhang B, Lu Q, Dai G, Zhou Y, Ye Q, Zhou Y, Tan WS. Enhancing mesenchymal stem cells cultivated on microcarriers in spinner flasks via impeller design optimization for aggregated suspensions. BIORESOUR BIOPROCESS 2023; 10:89. [PMID: 38647954 PMCID: PMC10992254 DOI: 10.1186/s40643-023-00707-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 11/16/2023] [Indexed: 04/25/2024] Open
Abstract
During the ex vivo expansion of umbilical cord-derived mesenchymal stem cells (hUCMSCs) in a stirred tank bioreactor, the formation of cell-microcarrier aggregates significantly affects cell proliferation and physiological activity, making it difficult to meet the quantity and quality requirements for in vitro research and clinical applications. In this study, computational fluid dynamic (CFD) simulations were used to investigate the effect of an impeller structure in a commercial spinner flask on flow field structure, aggregate formation, and cellular physiological activity. By designing a modified impeller, the aggregate size was reduced, which promoted cell proliferation and stemness maintenance. This study showed that increasing the stirring speed reduced the size of hUCMSC-microcarrier aggregates with the original impeller. However, it also inhibited cell proliferation, decreased activity, and led to spontaneous differentiation. Compared to low stirring speeds, high stirring speeds did not alter the radial flow characteristics and vortex distribution of the flow field, but did generate higher shear rates. The new impeller's design changed the flow field from radial to axial. The use of the novel impeller with an increased axial pumping rate (Qz) at a similar shear rate compared to the original impeller resulted in a 43.7% reduction in aggregate size, a 37.4% increase in cell density, and a better preservation of the expression of stemness markers (SOX2, OCT4 and NANOG). Increasing the Qz was a key factor in promoting aggregate suspension and size reduction. The results of this study have significant implications for the design of reactors, the optimisation of operating parameters, and the regulation of cellular physiological activity during MSC expansion.
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Affiliation(s)
- Botao Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Qiaohui Lu
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Gance Dai
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Yi Zhou
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Qian Ye
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Yan Zhou
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
| | - Wen-Song Tan
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
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Jiménez MF, Gómez-Hernández MT, Villarón EM, López-Parra M, Sánchez-Guijo F. Autologous mesenchymal stromal cells embedded with Tissucol Duo ® for prevention of air leak after anatomical lung resection: results of a prospective phase I/II clinical trial with long-term follow-up. Stem Cell Res Ther 2023; 14:313. [PMID: 37904229 PMCID: PMC10617222 DOI: 10.1186/s13287-023-03545-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 10/25/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND Prolonged air leak (PAL) is the most frequent complication after pulmonary resection. Several measures have been described to prevent the occurrence of PAL in high-risk patients, however, the potential role of mesenchymal stem cells (MSCs) applied in the parenchymal suture line to prevent postoperative air leak in this setting has not been fully addressed. OBJECTIVE To analyse the feasibility, safety and potential clinical efficacy of the implantation of autologous MSCs embedded in Tissucol Duo® as a prophylactic alternative to prevent postoperative prolonged air leak after pulmonary resection in high-risk patients. STUDY DESIGN Phase I/II single-arm prospective clinical trial. METHODS Six patients with high risk of PAL undergoing elective pulmonary resection were included. Autologous bone marrow-derived MSCs were expanded at our Good Manufacturing Practice (GMP) Facility and implanted (embedded in a Tissucol Duo® carrier) in the parenchymal suture line during pulmonary resection surgery. Patients were monitored in the early postoperative period and evaluated for possible complications or adverse reactions. In addition, all patients were followed-up to 5 years for clinical outcomes. RESULTS The median age of patients included was 66 years (range: 55-70 years), and male/female ratio was 5/1. Autologous MSCs were expanded in five cases, in one case MSCs expansion was insufficient. There were no adverse effects related to cell implantation. Regarding efficacy, median air leak duration was 0 days (range: 0-2 days). The incidence of PAL was nil. Radiologically, only one patient presented pneumothorax in the chest X-ray at discharge. No adverse effects related to the procedure were recorded during the follow-up. CONCLUSIONS The use of autologous MSCs for prevention of PAL in patients with high risk of PAL is feasible, safe and potentially effective. TRIAL REGISTRATION NO EudraCT: 2013-000535-27. CLINICALTRIALS gov idenfier: NCT02045745.
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Affiliation(s)
- Marcelo F Jiménez
- Service of Thoracic Surgery, Salamanca University Hospital, 37007, Salamanca, Spain
- Salamanca Institute of Biomedical Research (IBSAL), Salamanca, Spain
- University of Salamanca, Salamanca, Spain
| | - María Teresa Gómez-Hernández
- Service of Thoracic Surgery, Salamanca University Hospital, 37007, Salamanca, Spain.
- Salamanca Institute of Biomedical Research (IBSAL), Salamanca, Spain.
- University of Salamanca, Salamanca, Spain.
| | - Eva M Villarón
- Cell Therapy Area & Hematology Department, Salamanca University Hospital, Salamanca, Spain
- Network Centre for Regenerative Medicine and Cellular Therapy of Castilla y León, Salamanca, Spain
| | - Miriam López-Parra
- Cell Therapy Area & Hematology Department, Salamanca University Hospital, Salamanca, Spain
- Salamanca Institute of Biomedical Research (IBSAL), Salamanca, Spain
- Network Centre for Regenerative Medicine and Cellular Therapy of Castilla y León, Salamanca, Spain
| | - Fermín Sánchez-Guijo
- Cell Therapy Area & Hematology Department, Salamanca University Hospital, Salamanca, Spain
- Salamanca Institute of Biomedical Research (IBSAL), Salamanca, Spain
- University of Salamanca, Salamanca, Spain
- Network Centre for Regenerative Medicine and Cellular Therapy of Castilla y León, Salamanca, Spain
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Babaei H, Kheirollah A, Ranjbaran M, Sarkaki A, Adelipour M. Dose-dependent neuroprotective effects of adipose-derived mesenchymal stem cells on amyloid β-induced Alzheimer's disease in rats. Biochem Biophys Res Commun 2023; 678:62-67. [PMID: 37619312 DOI: 10.1016/j.bbrc.2023.08.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 08/17/2023] [Indexed: 08/26/2023]
Abstract
AIM Mesenchymal stem cells (MSCs) have emerged as an intriguing candidate in cell therapy for treating neurodegenerative diseases, including Alzheimer's disease (AD). To achieve the maximum efficiency of cell therapy, determining the optimal dose of MSCs is essential. This study was conducted to assess the dose-dependent therapeutic response of MSCs against pathological and behavioral AD-associated alterations. METHODS Aβ1-42 was injected intrahippocampally to establish an AD rat model. The MWM test was utilized to evaluate the animal's behavioral functions after receiving low and high doses of MSCs in the hippocampus region. ELISA and RT-qPCR were also employed to assess the concentration of markers related to antioxidant activity and inflammation and the gene expression related to apoptosis in the hippocampus region, respectively. RESULTS Low-dose MSC transplantation by increasing the concentrations of the antioxidant GSH, the anti-inflammatory cytokine IL-10, as well as by lowering the concentrations of TNF-α, and the expression levels of apoptotic factors (Bax and caspase 3), exerted a neuroprotective effect in the hippocampus of AD rats and relatively ameliorated spatial learning and memory impairments. However, increasing the dose of MSCs decreased the therapeutic benefits of these cells and had no significant effect on the recovery of behavioral disorders. CONCLUSION Our findings reveal the dose-dependent neuroprotective effect of MSCs in AD. The therapeutic response of MSCs to ameliorate the pathological and behavioral alterations associated with AD is attenuated when the dosage of MSCs is increased.
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Affiliation(s)
- Hossein Babaei
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Alireza Kheirollah
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mina Ranjbaran
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Sarkaki
- Department of Physiology, School of Medicine, Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Maryam Adelipour
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Physiology, School of Medicine, Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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20
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Budeus B, Unger K, Hess J, Sentek H, Klein D. Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts. Front Immunol 2023; 14:1270493. [PMID: 37822926 PMCID: PMC10562561 DOI: 10.3389/fimmu.2023.1270493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 08/30/2023] [Indexed: 10/13/2023] Open
Abstract
Introduction Mesenchymal stem cells (MSCs) are considered to be the most promising stem cell type for cell-based therapies in regenerative medicine. Based on their potential to home to diseased body sites following a therapeutically application, these cells could (i) differentiate then into organ-specific cell types to locally restore injured cells or, most prominently, (ii) foster tissue regeneration including immune modulations more indirectly by secretion of protective growth factors and cytokines. As tissue-resident stem cells of mesenchymal origin, these cells are morphologically and even molecularly- at least concerning the classical marker genes- indistinguishable from similar lineage cells, particularly fibroblasts. Methods Here we used microarray-based gene expression and global DNA methylation analyses as well as accompanying computational tools in order to specify differences between MSCs and fibroblasts, to further unravel potential identity genes and to highlight MSC signaling pathways with regard to their trophic and immunosuppressive action. Results We identified 1352 differentially expressed genes, of which in the MSCs there is a strong signature for e.g., KRAS signaling, known to play essential role in stemness maintenance, regulation of coagulation and complement being decisive for resolving inflammatory processes, as well as of wound healing particularly important for their regenerative capacity. Genes upregulated in fibroblasts addressed predominately transcription and biosynthetic processes and mapped morphological features of the tissue. Concerning the cellular identity, we specified the already known HOX code for MSCs, established a potential HOX code for fibroblasts, and linked certain HOX genes to functional cell-type-specific properties. Accompanied methylation profiles revealed numerous regions, especially in HOX genes, being differentially methylated, which might provide additional biomarker potential. Discussion Conclusively, transcriptomic together with epigenetic signatures can be successfully be used for the definition (cellular identity) of MSCs versus fibroblasts as well as for the determination of the superior functional properties of MSCs, such as their immunomodulatory potential.
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Affiliation(s)
- Bettina Budeus
- Institute for Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Kristian Unger
- Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany
- Clinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany
| | - Julia Hess
- Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany
- Clinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany
| | - Hanna Sentek
- Institute for Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Diana Klein
- Institute for Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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21
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Kuo YC, De S. Development of carbon dots to manage Alzheimer's disease and Parkinson's disease. J Taiwan Inst Chem Eng 2023. [DOI: 10.1016/j.jtice.2023.104799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
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22
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Giuli L, Santopaolo F, Pallozzi M, Pellegrino A, Coppola G, Gasbarrini A, Ponziani FR. Cellular therapies in liver and pancreatic diseases. Dig Liver Dis 2023; 55:563-579. [PMID: 36543708 DOI: 10.1016/j.dld.2022.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 10/21/2022] [Accepted: 11/22/2022] [Indexed: 04/29/2023]
Abstract
Over the past two decades, developments in regenerative medicine in gastroenterology have been greatly enhanced by the application of stem cells, which can self-replicate and differentiate into any somatic cell. The discovery of induced pluripotent stem cells has opened remarkable perspectives on tissue regeneration, including their use as a bridge to transplantation or as supportive therapy in patients with organ failure. The improvements in DNA manipulation and gene editing strategies have also allowed to clarify the physiopathology and to correct the phenotype of several monogenic diseases, both in vivo and in vitro. Further progress has been made with the development of three-dimensional cultures, known as organoids, which have demonstrated morphological and functional complexity comparable to that of a miniature organ. Hence, owing to its protean applications and potential benefits, cell and organoid transplantation has become a hot topic for the management of gastrointestinal diseases. In this review, we describe current knowledge on cell therapies in hepatology and pancreatology, providing insight into their future applications in regenerative medicine.
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Affiliation(s)
- Lucia Giuli
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Maria Pallozzi
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Antonio Pellegrino
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Gaetano Coppola
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy
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23
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Chenari A, Hazrati A, Hosseini AZ, Motiee M, Soudi S. The effect of mesenchymal stem cell-derived supernatant nasal administration on lung inflammation and immune response in BCG-vaccinated BALB/c mice. Life Sci 2023; 317:121465. [PMID: 36731650 DOI: 10.1016/j.lfs.2023.121465] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/26/2023] [Accepted: 01/27/2023] [Indexed: 02/01/2023]
Abstract
Mesenchymal stem cells (MSCs) are among the known cells that can control and modulate immune responses in different circumstances, including autoimmune diseases. Also, various studies have shown that they can prevent and reduces the pulmonary inflammation caused by infectious agents. In the case of tuberculosis and inflammation caused by BCG, the granuloma has destructive effects and improper orientation of the immune response. Therefore, it is possible to prevent airway damage by preventing harmful inflammatory responses and guiding the immune system responses. This study investigates the role of nasal administration of MSCs supernatant by designing an inflammatory model in the BALB/c mice lung with BCG. MSCs are isolated from mice adipose tissue in this study and evaluated for their phenotypic and differentiation properties. After the third passage, these cells' condition medium (CM) was collected. 20 mice were divided into four groups. Group 1 receive BCG (107 CFU in 5 ml volume for 15 min) nasal administration. Group 2 treated with CM, and group 3 initially were treated with CM (in 5 ml volume for 15 min) and, after 24 h, treated with BCG nasal administration. CM treatment was continued every five days for one month. The fourth group of mice was treated with PBS nasal administration of CM and BCG. One week after the last administration, the lung tissue of mice in each group was pathologically examined. In addition, secretion of IL1-β, IL-6, TNF-α, TGF-β, and IL-10 in the alveolar fluid and secretion of IL-4 and IFN-γ cytokines in the supernatant of splenocytes was evaluated by ELISA. The TNF-α/IL-10 ratio in the alveolar lung fluid of the BCG received group is 2/9 and decreased to 0.58 after successive CM treatment. Therefore, it can be concluded that inflammatory responses to BCG infection in the presence of CM are balanced and pave the way for the induction of effective immune responses by reducing lung tissue damage.
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Affiliation(s)
- Abolfazl Chenari
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Hazrati
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Zavaran Hosseini
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Mahdieh Motiee
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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24
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Weber L, Lee BS, Imboden S, Hsieh CJ, Lin NY. Phenotyping senescent mesenchymal stromal cells using AI image translation. CURRENT RESEARCH IN BIOTECHNOLOGY 2023; 5:100120. [PMID: 38045568 PMCID: PMC10691861 DOI: 10.1016/j.crbiot.2023.100120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) offer promising potential in biomedical research, clinical therapeutics, and immunomodulatory therapies due to their ease of isolation and multipotent, immunoprivileged, and immunosuppersive properties. Extensive efforts have focused on optimizing the cell isolation and culture methods to generate scalable, therapeutically-relevant MSCs for clinical applications. However, MSC-based therapies are often hindered by cell heterogeneity and inconsistency of therapeutic function caused, in part, by MSC senescence. As such, noninvasive and molecular-based MSC characterizations play an essential role in assuring the consistency of MSC functions. Here, we demonstrated that AI image translation algorithms can effectively predict immunofluorescence images of MSC senescence markers from phase contrast images. We showed that the expression level of senescence markers including senescence-associated beta-galactosidase (SABG), p16, p21, and p38 are accurately predicted by deep-learning models for Doxorubicin-induced MSC senescence, irradiation-induced MSC senescence, and replicative MSC senescence. Our AI model distinguished the non-senescent and senescent MSC populations and simultaneously captured the cell-to-cell variability within a population. Our microscopy-based phenotyping platform can be integrated with cell culture routines making it an easily accessible tool for MSC engineering and manufacturing.
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Affiliation(s)
- Leya Weber
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles 90095, CA, United States
| | - Brandon S. Lee
- Department of Bioengineering, University of California, Los Angeles 90095, CA, United States
| | - Sara Imboden
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles 90095, CA, United States
| | - Cho-Jui Hsieh
- Department of Computer Science, University of California, Los Angeles 90095, CA, United States
| | - Neil Y.C. Lin
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles 90095, CA, United States
- Department of Bioengineering, University of California, Los Angeles 90095, CA, United States
- California NanoSystems Institute, University of California, Los Angeles 90095, CA, United States
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles 90095, CA, United States
- Institute for Quantitative and Computational Biosciences, University of California, Los Angeles 90095, CA, United States
- Broad Stem Cell Center, University of California, Los Angeles 90095, CA, United States
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25
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Shen D, Wang H, Zhu H, Jiang C, Xie F, Zhang H, Lv Q, Liu Q, Wang Z, Qi N, Wang H. Pre-clinical efficacy evaluation of human umbilical cord mesenchymal stem cells for ischemic stroke. Front Immunol 2023; 13:1095469. [PMID: 36726973 PMCID: PMC9885855 DOI: 10.3389/fimmu.2022.1095469] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 12/29/2022] [Indexed: 01/15/2023] Open
Abstract
Objective This study explored the underlying therapeutic mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) for ischemic stroke (IS), and determined the optimal administration time windows and dose-effect relationship. Methods The levels of SDF-1α, IL-10, IL-6, TNF-α, BDNF, IL-1β, and VEGF-A factors in serum and brain tissue lysate were measured by ELISA. The pathological status of brain tissues was evaluated by Hematoxylin-Eosin (HE) staining, and apoptosis of nerve cells was detected by tunel. The protein expression of CXCR-4, NeuN, and Nestin in the brain tissues was assessed through immunofluorescence. The balance beam, forelimb muscle strength, and limb placement were tested on MCAO rats at different time points and doses. The infarct area of the rat brain tissues was measured at the end of the experiment. Results The hUCMSC treatment during the acute phase of MCAO significantly reduced the secretion of IL-6, TNF-α, IL-1β but increased IL-10 in serum, and the levels of SDF-α and BDNF in serum and brain tissues lysate were also increased. The pathological results showed that there were more neurons in the treatment group compared to the model group. Immunofluorescence assays showed that the expression of CXCR4、Nestin、NeuN was relatively higher than that in the model group. The d4 and d7 treatment significantly improves the motor function, promotes the recovery of forelimb muscle strength, increases the forelimb placement rate and reduces the scope of cerebral infarction, but the d14 treatment group has less therapeutic effect compared to the d4 and d7 treatment. The 2×107/kg treatment showed the best therapeutic effect, followed by the 1×107/kg treatment, and the worst is 0.5×107/kg treatment from the test of balance beam, forelimb muscle strength, limb placement and the infarct area of the rat brain tissues. Conclusion The hUCMSCs can inhibit the infiltration of inflammatory cells in the brain tissue, and promote the repair of brain tissue structure and function. Early intervention by injecting high-dose of hUCMSCs can significantly improve the recovery of neurological/motor function and reduce the size of cerebral infarction in rats.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Nianmin Qi
- *Correspondence: Hao Wang, ; Nianming Qi,
| | - Hao Wang
- *Correspondence: Hao Wang, ; Nianming Qi,
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26
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Nagai H, Miwa A, Yoneda K, Fujisawa K, Takami T. Optimizing the Seeding Density of Human Mononuclear Cells to Improve the Purity of Highly Proliferative Mesenchymal Stem Cells. BIOENGINEERING (BASEL, SWITZERLAND) 2023; 10:bioengineering10010102. [PMID: 36671674 PMCID: PMC9855129 DOI: 10.3390/bioengineering10010102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 12/29/2022] [Accepted: 01/06/2023] [Indexed: 01/15/2023]
Abstract
Mesenchymal stem cells (MSCs) hold considerable promise for regenerative medicine. Optimization of the seeding density of mononuclear cells (MNCs) improves the proliferative and differentiation potential of isolated MSCs. However, the underlying mechanism is unclear. We cultured human bone marrow MNCs at various seeding densities (4.0 × 104, 1.25 × 105, 2.5 × 105, 6.0 × 105, 1.25 × 106 cells/cm2) and examined MSC colony formation. At lower seeding densities (4.0 × 104, 1.25 × 105 cells/cm2), colonies varied in diameter and density, from dense to sparse. In these colonies, the proportion of highly proliferative MSCs increased over time. In contrast, lower proliferative MSCs enlarged more rapidly. Senescent cells were removed using a short detachment treatment. We found that these mechanisms increase the purity of highly proliferative MSCs. Thereafter, we compared MSCs isolated under optimized conditions with a higher density (1.25 × 106 cells/cm2). MSCs under optimized conditions exhibited significantly higher proliferative and differentiation potential into adipocytes and chondrocytes, except for osteocytes. We propose the following conditions to improve MSC quality: (1) optimizing MNC seeding density to form single-cell colonies; (2) adjusting incubation times to increase highly proliferative MSCs; and (3) establishing a detachment processing time that excludes senescent cells.
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Affiliation(s)
- Hiroyuki Nagai
- Shibuya Corporation, Kanazawa 920-8681, Ishikawa, Japan
- Department of Clinical Laboratory Science, Faculty of Health Science, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan
| | - Akihiro Miwa
- Shibuya Corporation, Kanazawa 920-8681, Ishikawa, Japan
| | - Kenji Yoneda
- Shibuya Corporation, Kanazawa 920-8681, Ishikawa, Japan
| | - Koichi Fujisawa
- Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Ube 755-8505, Yamaguchi, Japan
- Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu 807-8555, Fukuoka, Japan
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Ube 755-8505, Yamaguchi, Japan
- Correspondence:
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27
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Rajput S, Malviya R, Bahadur S, Puri D. Recent Updates on the Development of Therapeutics for the Targeted Treatment of Alzheimer's Disease. Curr Pharm Des 2023; 29:2802-2813. [PMID: 38018199 DOI: 10.2174/0113816128274618231105173031] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/08/2023] [Accepted: 10/03/2023] [Indexed: 11/30/2023]
Abstract
Alzheimer's disease (AD) is a complicated, multifaceted, irreversible, and incurable neurotoxic old age illness. Although NMDA (N-methyl D-aspartate)-receptor antagonists, cholinesterase repressors, and their pairings have been approved for the treatment, they are useful for short symptomatic relief. Researchers throughout the globe have been constantly working to uncover the therapy of Alzheimer's disease as new candidates must be determined, and newer treatment medicines must be developed. The aim of this review is to address recent advances in medication research along with new Alzheimer's disease therapy for diverse targets. Information was gathered utilizing a variety of internet resources as well as websites, such as ALZFORUM (alzforum.org) and clinicaltrials.gov. In contrast to other domains, the proposed medicines target amyloids (secretases, A42 generation, neuroinflammation, amyloid precipitation, and immunization), tau proteins (tau phosphorylation/aggregation and immunotherapy), and amyloid deposition. Despite tremendous advancement in our understanding of the underlying pathophysiology of Alzheimer's disease, the FDA (Food and Drug Administration) only approved aducanumab for diagnosis and treatment in 2003. Hence, novel treatment tactics are needed to find and develop therapeutic medicines to combat Alzheimer's disease.
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Affiliation(s)
- Shivam Rajput
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Shiv Bahadur
- Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Dinesh Puri
- School of Pharmacy, Graphic Era Hill University, Dehradun, India
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28
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Gudauskaitė G, Kairienė I, Ivaškienė T, Rascon J, Mobasheri A. Therapeutic Perspectives for the Clinical Application of Umbilical Cord Hematopoietic and Mesenchymal Stem Cells: Overcoming Complications Arising After Allogeneic Hematopoietic Stem Cell Transplantation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1409:111-126. [PMID: 35995905 DOI: 10.1007/5584_2022_726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
This review focuses on the therapeutic features of umbilical cord blood (UCB) cells as a source for allogeneic hematopoietic stem cell transplantation (aHSCT) in adult and child populations to treat malignant and nonmalignant hematologic diseases, genetic disorders, or pathologies of the immune system, when standard treatment (e.g., chemotherapy) is not effective or clinically contraindicated. In this article, we summarize the immunological properties and the advantages and disadvantages of using UCB stem cells and discuss a variety of treatment outcomes using different sources of stem cells from different donors both in adults and pediatric population. We also highlight the critical properties (total nucleated cell dose depending on HLA compatibility) of UCB cells that reach better survival rates, reveal the advantages of double versus single cord blood unit transplantation, and present recommendations from the most recent studies. Moreover, we summarize the mechanism of action and potential benefit of mesenchymal umbilical cord cells and indicate the most common posttransplantation complications.
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Affiliation(s)
- Greta Gudauskaitė
- State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
| | - Ignė Kairienė
- Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Tatjana Ivaškienė
- State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
| | - Jelena Rascon
- Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Ali Mobasheri
- State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
- Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
- World Health Organization Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, Liège, Belgium.
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29
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Sawyer SW, Takeda K, Alayoubi A, Mirdamadi E, Zidan A, Bauer SR, Degheidy H. 3D bioprinting optimization of human mesenchymal stromal cell laden gelatin-alginate-collagen bioink. Biomed Mater 2022; 18. [PMID: 36395510 DOI: 10.1088/1748-605x/aca3e7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/17/2022] [Indexed: 11/19/2022]
Abstract
3D bioprinting technology has gained increased attention in the regenerative medicine and tissue engineering communities over the past decade with their attempts to create functional living tissues and organsde novo. While tissues such as skin, bone, and cartilage have been successfully fabricated using 3D bioprinting, there are still many technical and process driven challenges that must be overcome before a complete tissue engineered solution is realized. Although there may never be a single adopted bioprinting process in the scientific community, adherence to optimized bioprinting protocols could reduce variability and improve precision with the goal of ensuring high quality printed constructs. Here, we report on the bioprinting of a gelatin-alginate-collagen bioink containing human mesenchymal stromal cells (hMSCs) which has been optimized to ensure printing consistency and reliability. The study consists of three phases: a pre-printing phase which focuses on bioink characterization; a printing phase which focuses on bioink extrudability/printability, construct stability, and printing accuracy; and a post-processing phase which focuses on the homogeneity and bioactivity of the encapsulated hMSC printed constructs. The results showed that eight identical constructs containing hMSCs could be reliably and accurately printed into stable cross-hatched structures with a single material preparation, and that batch-to-batch consistency was accurately maintained across all preparations. Analysis of the proliferation, morphology, and differentiation of encapsulated hMSCs within the printed constructs showed that cells were able to form large,interconnected colonies and were capable of robust adipogenic differentiation within 14 d of culturing.
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Affiliation(s)
- Stephen W Sawyer
- Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration, Silver Spring, MD, United States of America
| | - Kazuyo Takeda
- Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration, Silver Spring, MD, United States of America
| | - Alaadin Alayoubi
- Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration, Silver Spring, MD, United States of America
| | - Eman Mirdamadi
- Department of Bioengineering, University of Maryland, College Park, MD, United States of America
| | - Ahmed Zidan
- Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration, Silver Spring, MD, United States of America
| | - Steven R Bauer
- Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration, Silver Spring, MD, United States of America
| | - Heba Degheidy
- Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration, Silver Spring, MD, United States of America
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Gong SC, Yoon Y, Jung PY, Kim MY, Baik SK, Ryu H, Eom YW. Antifibrotic TSG-6 Expression Is Synergistically Increased in Both Cells during Coculture of Mesenchymal Stem Cells and Macrophages via the JAK/STAT Signaling Pathway. Int J Mol Sci 2022; 23:13122. [PMID: 36361907 PMCID: PMC9656625 DOI: 10.3390/ijms232113122] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/24/2022] [Accepted: 10/27/2022] [Indexed: 12/28/2022] Open
Abstract
The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β upregulate TNF-α-stimulated gene 6 (TSG-6); however, current knowledge about the optimal conditions for TSG-6 expression in mesenchymal stem cells (MSCs) is limited. Here, we investigated whether TSG-6 expression varies depending on the polarization state of macrophages co-cultured with adipose tissue-derived stem cells (ASCs) and analyzed the optimal conditions for TSG-6 expression in ASCs. TSG-6 expression increased in ASCs co-cultured with M0, M1, and M2 macrophages indirectly; among them, M1 macrophages resulted in the highest increase in TSG-6 expression in ASCs. TSG-6 expression in ASCs dramatically increased by combination (but not single) treatment of TNF-α, IL-1β, interferon-gamma (IFN-γ), and lipopolysaccharide (LPS). In addition, phosphorylation of signal transducer and activator of transcription (STAT) 1/3 was observed in response to IFN-γ and LPS treatment but not TNF-α and/or IL-1β. STAT1/3 activation synergistically increased TNF-α/IL-1β-dependent TSG-6 expression, and JAK inhibitors suppressed TSG-6 expression both in ASCs and macrophages. In LX-2 hepatic stellate cells, TSG-6 inhibited TGF-β-induced Smad3 phosphorylation, resulting in decreased α-smooth muscle actin (SMA) expression. Moreover, fibrotic activities of LX-2 cells induced by TGF-β were dramatically decreased after indirect co-culture with ASCs and M1 macrophages. These results suggest that a comprehensive inflammatory microenvironment may play an important role in determining the therapeutic properties of ASCs by increasing TSG-6 expression through STAT1/3 activation.
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Affiliation(s)
- Seong Chan Gong
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
| | - Yongdae Yoon
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
| | - Pil Young Jung
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
| | - Moon Young Kim
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
| | - Soon Koo Baik
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
| | - Hoon Ryu
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
| | - Young Woo Eom
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
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High throughput screening of mesenchymal stem cell lines using deep learning. Sci Rep 2022; 12:17507. [PMID: 36266301 PMCID: PMC9584889 DOI: 10.1038/s41598-022-21653-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 09/29/2022] [Indexed: 01/12/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are increasingly used as regenerative therapies for patients in the preclinical and clinical phases of various diseases. However, the main limitations of such therapies include functional heterogeneity and the lack of appropriate quality control (QC) methods for functional screening of MSC lines; thus, clinical outcomes are inconsistent. Recently, machine learning (ML)-based methods, in conjunction with single-cell morphological profiling, have been proposed as alternatives to conventional in vitro/vivo assays that evaluate MSC functions. Such methods perform in silico analyses of MSC functions by training ML algorithms to find highly nonlinear connections between MSC functions and morphology. Although such approaches are promising, they are limited in that extensive, high-content single-cell imaging is required; moreover, manually identified morphological features cannot be generalized to other experimental settings. To address these limitations, we propose an end-to-end deep learning (DL) framework for functional screening of MSC lines using live-cell microscopic images of MSC populations. We quantitatively evaluate various convolutional neural network (CNN) models and demonstrate that our method accurately classifies in vitro MSC lines to high/low multilineage differentiating stress-enduring (MUSE) cells markers from multiple donors. A total of 6,120 cell images were obtained from 8 MSC lines, and they were classified into two groups according to MUSE cell markers analyzed by immunofluorescence staining and FACS. The optimized DenseNet121 model showed area under the curve (AUC) 0.975, accuracy 0.922, F1 0.922, sensitivity 0.905, specificity 0.942, positive predictive value 0.940, and negative predictive value 0.908. Therefore, our DL-based framework is a convenient high-throughput method that could serve as an effective QC strategy in future clinical biomanufacturing processes.
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Liu X, Zhang G, Wei P, Hao L, Zhong L, Zhong K, Liu C, Liu P, Feng Q, Wang S, Zhang J, Tian R, Zhou L. 3D-printed collagen/silk fibroin/secretome derived from bFGF-pretreated HUCMSCs scaffolds enhanced therapeutic ability in canines traumatic brain injury model. Front Bioeng Biotechnol 2022; 10:995099. [PMID: 36091465 PMCID: PMC9449499 DOI: 10.3389/fbioe.2022.995099] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
The regeneration of brain tissue poses a great challenge because of the limited self-regenerative capabilities of neurons after traumatic brain injury (TBI). For this purpose, 3D-printed collagen/silk fibroin/secretome derived from human umbilical cord blood mesenchymal stem cells (HUCMSCs) pretreated with bFGF scaffolds (3D-CS-bFGF-ST) at a low temperature were prepared in this study. From an in vitro perspective, 3D-CS-bFGF-ST showed good biodegradation, appropriate mechanical properties, and good biocompatibility. In regard to vivo, during the tissue remodelling processes of TBI, the regeneration of brain tissues was obviously faster in the 3D-CS-bFGF-ST group than in the other two groups (3D-printed collagen/silk fibroin/secretome derived from human umbilical cord blood mesenchymal stem cells (3D-CS-ST) group and TBI group) by motor assay, histological analysis, and immunofluorescence assay. Satisfactory regeneration was achieved in the two 3D-printed scaffold-based groups at 6 months postsurgery, while the 3D-CS-bFGF-ST group showed a better outcome than the 3D-CS-ST group.
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Affiliation(s)
- Xiaoyin Liu
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Guijun Zhang
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Pan Wei
- Department of Neurosurgery, The First People’s Hospital of Long Quan yi District, Chengdu, China
| | - Lifang Hao
- Department of Radiology, Liao Cheng The Third People’s Hospital, Liaocheng, China
| | - Lin Zhong
- The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Kunhon Zhong
- State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Chang Liu
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Peng Liu
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Qingbo Feng
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Shan Wang
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
| | - Jianyong Zhang
- Department of General Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- *Correspondence: Jianyong Zhang, ; Rui Tian, ; Liangxue Zhou,
| | - Rui Tian
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- *Correspondence: Jianyong Zhang, ; Rui Tian, ; Liangxue Zhou,
| | - Liangxue Zhou
- Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- *Correspondence: Jianyong Zhang, ; Rui Tian, ; Liangxue Zhou,
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Morello W, Budelli S, Bernstein DA, Montemurro T, Montelatici E, Lavazza C, Ghio L, Edefonti A, Peruzzi L, Molino D, Benetti E, Gianoglio B, Mehmeti F, Catenacci L, Rotella J, Tamburello C, Moretta A, Lazzari L, Giordano R, Prati D, Montini G. First clinical application of cord blood mesenchymal stromal cells in children with multi-drug resistant nephrotic syndrome. STEM CELL RESEARCH & THERAPY 2022; 13:420. [PMID: 35986374 PMCID: PMC9389735 DOI: 10.1186/s13287-022-03112-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 08/03/2022] [Indexed: 12/02/2022]
Abstract
Background and objectives Children with multi-drug resistant idiopathic nephrotic syndrome (MDR-INS) usually progress to end-stage kidney disease with a consistent risk of disease recurrence after transplantation. New therapeutic options are needed for these patients. Mesenchymal stromal cells (MSCs) are multipotential non-hematopoietic cells with several immunomodulatory properties and growing clinical applications. Cord blood-derived MSC have peculiar anti-inflammatory and immunosuppressive properties. We aimed at assessing safety and efficacy of cord-blood-derived MSCs (CB-MSCs) in children with MDR-INS. Design, setting, participants Prospective, open-label, single arm phase I–II pilot study. Pediatric patients with MDR-INS, resistant to at least two lines of therapy, were enrolled. Allogenic CB-MSCs were administered intravenously on days 0, 14, and 21 at a dose of 1.5 × 106 cells/kg. Patients were followed for at least 12 months. The primary outcomes were safety and toxicity. The secondary outcome was remission at 12 months evaluated by urinary protein/urinary creatinine ratio (uPr/uCr). Circulating regulatory T cells (Tregs) were monitored. Results Eleven pediatric patients with MDR-INS (10 females, median age 13 years) resistant to a median of 3 previous lines of therapy were enrolled. All patients completed the CB-MSC infusion schedule. No patient experienced any infusion-related adverse event or toxicity. Nine patients were assessable for efficacy. At the 12 months follow-up after the treatment, the median uPr/uCr did not change significantly from baseline (8.13 vs. 9.07; p = 0.98), while 3 patients were in partial or complete remission. A lower baseline uPr/uCr was a predictor of remission (2.55 vs. 8.74; p = 0.0238). Tregs count was not associated with CB-MSCs therapy. Conclusions CB-MSCs are safe and may have a role in the immunosuppressive therapy of pediatric patients with MDR-INS. This preliminary experience paves the way toward further phase II studies addressing MSC efficacy in immune-mediated kidney diseases. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03112-7.
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Cellular Therapies in Pediatric Liver Diseases. Cells 2022; 11:cells11162483. [PMID: 36010561 PMCID: PMC9406752 DOI: 10.3390/cells11162483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/30/2022] [Accepted: 08/06/2022] [Indexed: 11/16/2022] Open
Abstract
Liver transplantation is the gold standard for the treatment of pediatric end-stage liver disease and liver based metabolic disorders. Although liver transplant is successful, its wider application is limited by shortage of donor organs, surgical complications, need for life long immunosuppressive medication and its associated complications. Cellular therapies such as hepatocytes and mesenchymal stromal cells (MSCs) are currently emerging as an attractive alternative to liver transplantation. The aim of this review is to present the existing world experience in hepatocyte and MSC transplantation and the potential for future effective applications of these modalities of treatment.
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35
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Abu-El-Rub E, Khasawneh RR, Almahasneh F. Prodigious therapeutic effects of combining mesenchymal stem cells with magnetic nanoparticles. World J Stem Cells 2022; 14:513-526. [PMID: 36157526 PMCID: PMC9350622 DOI: 10.4252/wjsc.v14.i7.513] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/18/2022] [Accepted: 06/22/2022] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have gained wide-ranging reputation in the medical research community due to their promising regenerative abilities. MSCs can be isolated from various resources mostly bone marrow, Adipose tissues and Umbilical cord. Huge advances have been achieved in comprehending the possible mechanisms underlying the therapeutic functions of MSCs. Despite the proven role of MSCs in repairing and healing of many disease modalities, many hurdles hinder the transferring of these cells in the clinical settings. Among the most reported problems encountering MSCs therapy in vivo are loss of tracking signal post-transplantation, insufficient migration, homing and engraftment post-infusion, and undesirable differentiation at the site of injury. Magnetic nano particles (MNPs) have been used widely for various biomedical applications. MNPs have a metallic core stabilized by an outer coating material and their ma gnetic properties can be modulated by an external magnetic field. These magnetic properties of MNPs were found to enhance the quality of diagnostic imaging procedures and can be used to create a carrying system for targeted delivery of therapeutic substances mainly drug, genes and stem cells. Several studies highlighted the advantageous outcomes of combining MSCs with MNPs in potentiating their tracking, monitoring, homing, engraftment and differentiation. In this review, we will discuss the role of MNPs in promoting the therapeutic profile of MSCs which may improve the success rate of MSCs transplantation and solve many challenges that delay their clinical applicability.
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Affiliation(s)
- Ejlal Abu-El-Rub
- Department of Physiology and Pathophysiology, Yarmouk University, Irbid 21163, Jordan
| | - Ramada R Khasawneh
- Department of Anatomy and Histology, Yarmouk University, Irbid 21163, Jordan.
| | - Fatimah Almahasneh
- Department of Physiology and Pathophysiology, Yarmouk University, Irbid 21163, Jordan
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36
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Hayun Y, Yaacobi DS, Shachar T, Harats M, Grush AE, Olshinka A. Novel Technologies in Chronic Wound Care. Semin Plast Surg 2022; 36:75-82. [DOI: 10.1055/s-0042-1749095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
AbstractIn Israel, 20% of wounds do not progress to full healing under treatment with conservative technologies of which 1 to 2% are eventually defined as chronic wounds. Chronic wounds are a complex health burden for patients and pose considerable therapeutic and budgetary burden on health systems. The causes of chronic wounds include systemic and local factors. Initial treatment involves the usual therapeutic means, but as healing does not progress, more advanced therapeutic technologies are used. Undoubtedly, advanced means, such as negative pressure systems, and advanced technologies, such as oxygen systems and micrografts, have vastly improved the treatment of chronic wounds. Our service specializes in treating ulcers and difficult-to-heal wounds while providing a multiprofessional medical response. Herein, we present our experience and protocols in treating chronic wounds using a variety of advanced dressings and technologies.
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Affiliation(s)
- Yehiel Hayun
- Department of Plastic Surgery and Burns, Rabin Medical Center—Beilinson Hospital, Petach Tikva, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dafna Shilo Yaacobi
- Department of Plastic Surgery and Burns, Rabin Medical Center—Beilinson Hospital, Petach Tikva, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tal Shachar
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Moti Harats
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The National Burn Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Andrew E. Grush
- Division of Plastic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
- Division of Plastic Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas
| | - Asaf Olshinka
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Plastic Surgery and Burns Unit, Schneider Children's Medical Center, Petach Tikva, Israel
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Zhou L, Zhu H, Bai X, Huang J, Chen Y, Wen J, Li X, Wu B, Tan Y, Tian M, Ren J, Li M, Yang Q. Potential mechanisms and therapeutic targets of mesenchymal stem cell transplantation for ischemic stroke. Stem Cell Res Ther 2022; 13:195. [PMID: 35551643 PMCID: PMC9096773 DOI: 10.1186/s13287-022-02876-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 04/25/2022] [Indexed: 12/25/2022] Open
Abstract
Ischemic stroke is one of the major causes of death and disability in the world. Currently, most patients cannot choose intravenous thrombolysis or intravascular mechanical thrombectomy because of narrow therapeutic windows and severe complications. Stem cell transplantation is an emerging treatment and has been studied in various central nervous system diseases. Animal and clinical studies showed that transplantation of mesenchymal stem cells (MSCs) could alleviate neurological deficits and bring hope for ischemic stroke treatment. This article reviewed biological characteristics, safety, feasibility and efficacy of MSCs therapy, potential therapeutic targets of MSCs, and production process of Good Manufacturing Practices-grade MSCs, to explore the potential therapeutic targets of MSCs in the process of production and use and provide new therapeutic directions for ischemic stroke.
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Affiliation(s)
- Li Zhou
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Huimin Zhu
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Xue Bai
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.,Department of Neurology, The First People's Hospital of Neijiang, Sichuan, 64100, China
| | - Jiagui Huang
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Yue Chen
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Jun Wen
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Xuemei Li
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Bowen Wu
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Yongjun Tan
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Mingfen Tian
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Jiangxia Ren
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Mengxia Li
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Qin Yang
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
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Robinson AM, Stavely R, Miller S, Eri R, Nurgali K. Mesenchymal stem cell treatment for enteric neuropathy in the Winnie mouse model of spontaneous chronic colitis. Cell Tissue Res 2022; 389:41-70. [PMID: 35536444 DOI: 10.1007/s00441-022-03633-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 04/26/2022] [Indexed: 11/30/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic gut inflammation with periods of acute flares and remission. Beneficial effects of a single dose of mesenchymal stem cell (MSC)-based treatment have been demonstrated in acute models of colitis. No studies investigated therapeutic effects of MSCs for the attenuation of enteric neuropathy in a chronic model of colitis. The short and long-term effects of MSC treatment in modulating inflammation and damage to the enteric nervous system (ENS) were studied in the Winnie mouse model of spontaneous chronic colitis highly representative of human IBD. Winnie mice received a single dose of either 1 × 106 human bone marrow-derived MSCs or 100µL PBS by intracolonic enema. C57BL/6 mice received 100µL PBS. Colon tissues were collected at 3 and 60 days post MSC administration to evaluate the short-term and long-term effects of MSCs on inflammation and enteric neuropathy by histological and immunohistochemical analyses. In a separate set of experiments, multiple treatments with 4 × 106 and 2 × 106 MSCs were performed and tissue collected at 3 days post treatment. Chronic intestinal inflammation in Winnie mice was associated with persistent diarrhea, perianal bleeding, morphological changes, and immune cell infiltration in the colon. Significant changes to the ENS, including impairment of cholinergic, noradrenergic and sensory innervation, and myenteric neuronal loss were prominent in Winnie mice. Treatment with a single dose of bone marrow-derived MSCs was ineffective in attenuating chronic inflammation and enteric neuropathy in Winnie.
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Affiliation(s)
- Ainsley M Robinson
- Institute for Health and Sport, Victoria University; Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia
| | - Rhian Stavely
- Institute for Health and Sport, Victoria University; Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia.,Department of Pediatric Surgery, Pediatric Surgery Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Sarah Miller
- Institute for Health and Sport, Victoria University; Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia
| | - Rajaraman Eri
- University of Tasmania, School of Health Sciences, Launceston, TAS, Australia
| | - Kulmira Nurgali
- Institute for Health and Sport, Victoria University; Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia. .,Department of Medicine Western Health, The University of Melbourne, Melbourne, VIC, Australia. .,Regenerative Medicine and Stem Cells Program, Australian Institute of Musculoskeletal Science (AIMSS), Melbourne, VIC, Australia.
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Fu Z, Chu Y, Geng X, Ma Y, Chi K, Song C, Liao S, Hong Q, Wu D, Wang Y. Artificial Kidney Capsule Packed with Mesenchymal Stem Cell-Laden Hydrogel for the Treatment of Rhabdomyolysis-Induced Acute Kidney Injury. ACS Biomater Sci Eng 2022; 8:1726-1734. [PMID: 35302761 DOI: 10.1021/acsbiomaterials.1c01595] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Acute kidney injury (AKI) has emerged as a major public health problem affecting millions of people worldwide without specific and satisfactory therapies due to the lack of an effective delivery approach. In the past few decades, hydrogels present infinite potential in localized drug delivery, while their poor adhesion to moist tissue and isotropic diffusion character always restrict the therapeutic efficiency and may lead to unwanted side effects. Herein, we proposed a novel therapeutic strategy for AKI via a customizable artificial kidney capsule (AKC) together with a mesenchymal stem cell (MSC)-laden hydrogel. Specifically, an elastic capsule owning an inner chamber with the same size and shape as the kidney is designed and fabricated through three-dimensional (3D) modeling and printing, serving as an outer wrap for kidney and cell-laden hydrogels. According to the in vitro experiment, the excellent biocompatibility of gelatin-based hydrogel ensures viability and proliferation of MSCs. In vivo mice experiments proved that this concept of AKC-assisted kidney drug delivery could efficiently reduce epithelial cell apoptosis and minimize the damage of the renal tubular structure for mice suffering AKI. Such a strategy not only provides a promising alternative in the treatment of AKI but also offers a feasible and versatile approach for the repair and recovery of other organs.
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Affiliation(s)
- Zhangning Fu
- Medical School of Chinese PLA, Beijing 100853, China.,Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China
| | - Yanji Chu
- Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing 100872, China
| | - Xiaodong Geng
- Medical School of Chinese PLA, Beijing 100853, China.,Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.,Beidaihe Rehabilitation and Recuperation Center, Chinese People's Liberation Army Joint Logistics Support Force, Qinhuangdao 066100, China
| | - Yingchao Ma
- Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing 100872, China
| | - Kun Chi
- Medical School of Chinese PLA, Beijing 100853, China.,Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China
| | - Chengcheng Song
- Medical School of Chinese PLA, Beijing 100853, China.,Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China
| | - Shenglong Liao
- Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing 100872, China
| | - Quan Hong
- Medical School of Chinese PLA, Beijing 100853, China.,Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China
| | - Di Wu
- Medical School of Chinese PLA, Beijing 100853, China.,Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China
| | - Yapei Wang
- Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing 100872, China
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Efficacy and Safety of Mesenchymal Stem Cell Transplantation in the Treatment of Autoimmune Diseases (Rheumatoid Arthritis, Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Multiple Sclerosis, and Ankylosing Spondylitis): A Systematic Review and Meta-Analysis of Randomized Controlled Trial. Stem Cells Int 2022; 2022:9463314. [PMID: 35371265 PMCID: PMC8970953 DOI: 10.1155/2022/9463314] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 12/05/2021] [Accepted: 01/04/2022] [Indexed: 01/30/2023] Open
Abstract
Objective To evaluate the efficacy and safety of mesenchymal stem cell (MSC) transplantation in the treatment of autoimmune diseases. Methods The Chinese and English databases were searched for clinical research on the treatment of autoimmune diseases with mesenchymal stem cells. The search time range is from a self-built database to October 1, 2021. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted data, and evaluated the bias of the included studies. RevMan 5.3 analysis software was used for meta-analysis. Results A total of 18 RCTs involving 5 autoimmune diseases were included. The 5 autoimmune disease were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease, ankylosing spondylitis, and multiple sclerosis. For RA, the current randomized controlled trials (RCTs) still believe that stem cell transplantation may reduce disease activity, improve the clinical symptoms (such as DAS28), and the percentage of CD4+CD 25+Foxp3+Tregs in the response group increased and the percentage of CD4+IL-17A+Th17 cells decreased. The total clinical effective rate of RA is 54%. For SLE, the results showed that mesenchymal stem cell transplantation may improve SLEDAI [-2.18 (-3.62, -0.75), P = 0.003], urine protein [-0.93 (-1.04, -0.81), P < 0.00001], and complement C3 [0.31 (0.19, 0.42), P < 0.00001]. For inflammatory bowel disease, the results showed that mesenchymal stem cell transplantation may improve clinical efficacy [2.50 (1.07, 5.84), P = 0.03]. For ankylosing spondylitis, MSC treatment for 6 months may increase the total effective rate; reduce erythrocyte sedimentation rate, intercellular adhesion molecules, and serum TNF-α; and improve pain and activity. For multiple sclerosis, the current research results are still controversial, so more RCTs are needed to amend or confirm the conclusions. No obvious adverse events of mesenchymal stem cell transplantation were found in all RCTs. Conclusion MSCs have a certain effect on different autoimmune diseases, but more RCTs are needed to further modify or confirm the conclusion.
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Li Y, Hao J, Hu Z, Yang YG, Zhou Q, Sun L, Wu J. Current status of clinical trials assessing mesenchymal stem cell therapy for graft versus host disease: a systematic review. Stem Cell Res Ther 2022; 13:93. [PMID: 35246235 PMCID: PMC8895864 DOI: 10.1186/s13287-022-02751-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 01/31/2022] [Indexed: 12/11/2022] Open
Abstract
Background Graft-versus-host disease (GVHD) is a common fatal complication of hematopoietic stem cell transplantation (HSCT), where steroids are used as a treatment option. However, there are currently no second-line treatments for patients that develop steroid-resistance (SR). Mesenchymal stem cells (MSCs) have immunomodulatory functions and can exert immunosuppressive effects on the inflammatory microenvironment. A large number of in vitro experiments have confirmed that MSCs can significantly inhibit the proliferation or activation of innate and adaptive immune cells. In a mouse model of GVHD, MSCs improved weight loss and increased survival rate. Therefore, there is great promise for the clinical translation of MSCs for the prevention or treatment of GVHD, and several clinical trials have already been conducted to date. Main body In this study, we searched multiple databases and found 79 clinical trials involving the use of MSCs to prevent or treat GVHD and summarized the characteristics of these clinical trials, including study design, phase, status, and locations. We analyzed the results of these clinical trials, including the response and survival rates, to enable researchers to obtain a comprehensive understanding of the field’s progress, challenges, limitations, and future development trends. Additionally, factors that might result in inconsistencies in clinical trial results were discussed. Conclusion In this study, we attempted to analyze the clinical trials for MSCs in GVHD, identify the most suitable group of patients for MSC therapy, and provide a new perspective for the design of such trials in the future. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02751-0.
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Affiliation(s)
- Ying Li
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, 130061, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, 130061, China.,Department of Gastroenterology, The First Hospital, Jilin University, Changchun, 130021, China
| | - Jie Hao
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.,Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.,National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing, 100101, China
| | - Zheng Hu
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, 130061, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, 130061, China
| | - Yong-Guang Yang
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, 130061, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, 130061, China.,International Center of Future Science, Jilin University, Changchun, 130021, China
| | - Qi Zhou
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. .,Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. .,National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing, 100101, China. .,University of Chinese Academy of Sciences, Beijing, 100049, China.
| | - Liguang Sun
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, 130061, China. .,National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, 130061, China.
| | - Jun Wu
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. .,Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. .,National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing, 100101, China.
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Szewc M, Radzikowska-Bűchner E, Wdowiak P, Kozak J, Kuszta P, Niezabitowska E, Matysiak J, Kubiński K, Masłyk M. MSCs as Tumor-Specific Vectors for the Delivery of Anticancer Agents-A Potential Therapeutic Strategy in Cancer Diseases: Perspectives for Quinazoline Derivatives. Int J Mol Sci 2022; 23:2745. [PMID: 35269887 PMCID: PMC8911180 DOI: 10.3390/ijms23052745] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are considered to be a powerful tool in the treatment of various diseases. Scientists are particularly interested in the possibility of using MSCs in cancer therapy. The research carried out so far has shown that MSCs possess both potential pro-oncogenic and anti-oncogenic properties. It has been confirmed that MSCs can regulate tumor cell growth through a paracrine mechanism, and molecules secreted by MSCs can promote or block a variety of signaling pathways. These findings may be crucial in the development of new MSC-based cell therapeutic strategies. The abilities of MSCs such as tumor tropism, deep migration and immune evasion have evoked considerable interest in their use as tumor-specific vectors for small-molecule anticancer agents. Studies have shown that MSCs can be successfully loaded with chemotherapeutic drugs such as gemcitabine and paclitaxel, and can release them at the site of primary and metastatic neoplasms. The inhibitory effect of MSCs loaded with anti-cancer agents on the proliferation of cancer cells has also been observed. However, not all known chemotherapeutic agents can be used in this approach, mainly due to their cytotoxicity towards MSCs and insufficient loading and release capacity. Quinazoline derivatives appear to be an attractive choice for this therapeutic solution due to their biological and pharmacological properties. There are several quinazolines that have been approved for clinical use as anticancer drugs by the US Food and Drug Administration (FDA). It gives hope that the synthesis of new quinazoline derivatives and the development of methods of their application may contribute to the establishment of highly effective therapies for oncological patients. However, a deeper understanding of interactions between MSCs and tumor cells, and the exploration of the possibilities of using quinazoline derivatives in MSC-based therapy is necessary to achieve this goal. The aim of this review is to discuss the prospects for using MSC-based cell therapy in cancer treatment and the potential use of quinazolines in this procedure.
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Affiliation(s)
- Monika Szewc
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (P.W.); (J.K.); (P.K.)
| | - Elżbieta Radzikowska-Bűchner
- Department of Plastic, Reconstructive and Maxillary Surgery, Central Clinical Hospital MSWiA, 02-507 Warsaw, Poland;
| | - Paulina Wdowiak
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (P.W.); (J.K.); (P.K.)
| | - Joanna Kozak
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (P.W.); (J.K.); (P.K.)
| | - Piotr Kuszta
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (P.W.); (J.K.); (P.K.)
| | - Ewa Niezabitowska
- Department of Urology and Urological Oncology, Multidisciplinary Hospital in Lublin, 20-400 Lublin, Poland;
| | - Joanna Matysiak
- Department of Chemistry, University of Life Sciences in Lublin, 20-950 Lublin, Poland;
| | - Konrad Kubiński
- Department of Molecular Biology, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland;
| | - Maciej Masłyk
- Department of Molecular Biology, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland;
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Jeyaraman M, Bingi SK, Muthu S, Jeyaraman N, Packkyarathinam RP, Ranjan R, Sharma S, Jha SK, Khanna M, Rajendran SNS, Rajendran RL, Gangadaran P. Impact of the Process Variables on the Yield of Mesenchymal Stromal Cells from Bone Marrow Aspirate Concentrate. Bioengineering (Basel) 2022; 9:57. [PMID: 35200410 PMCID: PMC8869489 DOI: 10.3390/bioengineering9020057] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/18/2022] [Accepted: 01/20/2022] [Indexed: 02/07/2023] Open
Abstract
Human bone marrow (BM) has been highlighted as a promising source of mesenchymal stromal cells (MSCs) containing various growth factors and cytokines that can be potentially utilized in regenerative procedures involving cartilage and bone. However, the proportion of MSCs in the nucleated cell population of BM is only around 0.001% to 0.01% thereby making the harvesting and processing technique crucial for obtaining optimal results upon its use in various regenerative processes. Although several studies in the literature have given encouraging results on the utility of BM aspiration concentrate (BMAC) in various regenerative procedures, there is a lack of consensus concerning the harvesting variables such as choice of anesthetic agent to be used, site of harvest, size of the syringe to be used, anticoagulant of choice, and processing variables such as centrifugation time, and speed. In this review article, we aim to discuss the variables in the harvesting and processing technique of BMAC and their impact on the yield of MSCs in the final concentrate obtained from them.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Orthopaedics, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, India;
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India;
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, India; (S.K.B.); (M.K.)
| | - Shiva Kumar Bingi
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, India; (S.K.B.); (M.K.)
- Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow 226010, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India;
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, India; (S.K.B.); (M.K.)
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624304, India
| | - Naveen Jeyaraman
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, India; (S.K.B.); (M.K.)
- Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow 226010, India
- Fellow in Joint Replacement, Department of Orthopaedics, Atlas Hospitals, Tiruchirappalli 620002, India
| | | | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida 201310, India;
| | - Shilpa Sharma
- Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India;
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India;
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, India; (S.K.B.); (M.K.)
- Department of Orthopaedics, Prasad Institute of Medical Sciences, Lucknow 226401, India
| | - Sree Naga Sowndary Rajendran
- Department of Medicine, Sri Venkateshwaraa Medical College Hospital and Research Centre, Puducherry 605102, India;
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea;
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
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44
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Mesenchymal Stem Cell-Based Therapy as a New Approach for the Treatment of Systemic Sclerosis. Clin Rev Allergy Immunol 2022; 64:284-320. [PMID: 35031958 DOI: 10.1007/s12016-021-08892-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2021] [Indexed: 12/13/2022]
Abstract
Systemic sclerosis (SSc) is an intractable autoimmune disease with unmet medical needs. Conventional immunosuppressive therapies have modest efficacy and obvious side effects. Targeted therapies with small molecules and antibodies remain under investigation in small pilot studies. The major breakthrough was the development of autologous haematopoietic stem cell transplantation (AHSCT) to treat refractory SSc with rapidly progressive internal organ involvement. However, AHSCT is contraindicated in patients with advanced visceral involvement. Mesenchymal stem cells (MSCs) which are characterized by immunosuppressive, antifibrotic and proangiogenic capabilities may be a promising alternative option for the treatment of SSc. Multiple preclinical and clinical studies on the use of MSCs to treat SSc are underway. However, there are several unresolved limitations and safety concerns of MSC transplantation, such as immune rejections and risks of tumour formation, respectively. Since the major therapeutic potential of MSCs has been ascribed to their paracrine signalling, the use of MSC-derived extracellular vesicles (EVs)/secretomes/exosomes as a "cell-free" therapy might be an alternative option to circumvent the limitations of MSC-based therapies. In the present review, we overview the current knowledge regarding the therapeutic efficacy of MSCs in SSc, focusing on progresses reported in preclinical and clinical studies using MSCs, as well as challenges and future directions of MSC transplantation as a treatment option for patients with SSc.
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45
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Shin MJ, Park JY, Lee DH, Khang D. Stem Cell Mimicking Nanoencapsulation for Targeting Arthritis. Int J Nanomedicine 2022; 16:8485-8507. [PMID: 35002240 PMCID: PMC8725870 DOI: 10.2147/ijn.s334298] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 12/05/2021] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are considered a promising regenerative therapy due to their ability to migrate toward damaged tissues. The homing ability of MSCs is unique compared with that of non-migrating cells and MSCs are considered promising therapeutic vectors for targeting major cells in many pathophysiological sites. MSCs have many advantages in the treatment of malignant diseases, particularly rheumatoid arthritis (RA). RA is a representative autoimmune disease that primarily affects joints, and secreted chemokines in the joints are well recognized by MSCs following their migration to the joints. Furthermore, MSCs can regulate the inflammatory process and repair damaged cells in the joints. However, the functionality and migration ability of MSCs injected in vivo still show insufficient. The targeting ability and migration efficiency of MSCs can be enhanced by genetic engineering or modification, eg, overexpressing chemokine receptors or migration-related genes, thus maximizing their therapeutic effect. However, there are concerns about genetic changes due to the increased probability of oncogenesis resulting from genome integration of the viral vector, and thus, clinical application is limited. Furthermore, it is suspected that administering MSCs can promote tumor growth and metastasis in xenograft and orthotopic models. For this reason, MSC mimicking nanoencapsulations are an alternative strategy that does not involve using MSCs or bioengineered MSCs. MSC mimicking nanoencapsulations consist of MSC membrane-coated nanoparticles, MSC-derived exosomes and artificial ectosomes, and MSC membrane-fused liposomes with natural or genetically engineered MSC membranes. MSC mimicking nanoencapsulations not only retain the targeting ability of MSCs but also have many advantages in terms of targeted drug delivery. Specifically, MSC mimicking nanoencapsulations are capable of encapsulating drugs with various components, including chemotherapeutic agents, nucleic acids, and proteins. Furthermore, there are fewer concerns over safety issues on MSC mimicking nanoencapsulations associated with mutagenesis even when using genetically engineered MSCs, because MSC mimicking nanoencapsulations use only the membrane fraction of MSCs. Genetic engineering is a promising route in clinical settings, where nano-encapsulated technology strategies are combined. In this review, the mechanism underlying MSC homing and the advantages of MSC mimicking nanoencapsulations are discussed. In addition, genetic engineering of MSCs and MSC mimicking nanoencapsulation is described as a promising strategy for the treatment of immune-related diseases.
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Affiliation(s)
- Min Jun Shin
- Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, South Korea.,Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, South Korea
| | - Jun Young Park
- Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, South Korea.,Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, South Korea
| | - Dae Ho Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, 21999, South Korea.,Department of Internal Medicine, Gachon University College of Medicine, Incheon, 21999, South Korea
| | - Dongwoo Khang
- Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, South Korea.,Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, South Korea.,Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, South Korea
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46
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Regenerative Medicine Application of Mesenchymal Stem Cells. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1387:25-42. [DOI: 10.1007/5584_2022_713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Yuan X, Li L, Liu H, Luo J, Zhao Y, Pan C, Zhang X, Chen Y, Gou M. Strategies for improving adipose-derived stem cells for tissue regeneration. BURNS & TRAUMA 2022; 10:tkac028. [PMID: 35992369 PMCID: PMC9382096 DOI: 10.1093/burnst/tkac028] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 02/27/2022] [Indexed: 11/13/2022]
Abstract
Abstract
Adipose-derived stem cells (ADSCs) have promising applications in tissue regeneration. Currently, there are only a few ADSC products that have been approved for clinical use. The clinical application of ADSCs still faces many challenges. Here, we review emerging strategies to improve the therapeutic efficacy of ADSCs in tissue regeneration. First, a great quantity of cells is often needed for the stem cell therapies, which requires the advanced cell expansion technologies. In addition cell-derived products are also required for the development of ‘cell-free’ therapies to overcome the drawbacks of cell-based therapies. Second, it is necessary to strengthen the regenerative functions of ADSCs, including viability, differentiation and paracrine ability, for the tissue repair and regeneration required for different physiological and pathophysiological conditions. Third, poor delivery efficiency also restricts the therapeutic effect of ADSCs. Effective methods to improve cell delivery include alleviating harsh microenvironments, enhancing targeting ability and prolonging cell retention. Moreover, we also point out some critical issues about the sources, effectiveness and safety of ADSCs. With these advanced strategies to improve the therapeutic efficacy of ADSCs, ADSC-based treatment holds great promise for clinical applications in tissue regeneration.
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Affiliation(s)
- Xin Yuan
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University , Chengdu, 610041, China
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Li Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Haofan Liu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Jing Luo
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Yongchao Zhao
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Cheng Pan
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Xue Zhang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Yuwen Chen
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Maling Gou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University , Chengdu, 610041, China
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48
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Haseli M, Castilla-Casadiego DA, Pinzon-Herrera L, Hillsley A, Miranda-Munoz KA, Sivaraman S, Rosales AM, Rao RR, Almodovar J. Immunomodulatory functions of human mesenchymal stromal cells are enhanced when cultured on HEP/COL multilayers supplemented with interferon-gamma. Mater Today Bio 2022; 13:100194. [PMID: 35005599 PMCID: PMC8715375 DOI: 10.1016/j.mtbio.2021.100194] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/20/2021] [Accepted: 12/22/2021] [Indexed: 12/15/2022] Open
Abstract
Human mesenchymal stromal cells (hMSCs) are multipotent cells that have been proposed for cell therapies due to their immunosuppressive capacity that can be enhanced in the presence of interferon-gamma (IFN-γ). In this study, multilayers of heparin (HEP) and collagen (COL) (HEP/COL) were used as a bioactive surface to enhance the immunomodulatory activity of hMSCs using soluble IFN-γ. Multilayers were formed, via layer-by-layer assembly, varying the final layer between COL and HEP and supplemented with IFN-γ in the culture medium. We evaluated the viability, adhesion, real-time growth, differentiation, and immunomodulatory activity of hMSCs on (HEP/COL) multilayers. HMSCs viability, adhesion, and growth were superior when cultured on (HEP/COL) multilayers compared to tissue culture plastic. We also confirmed that hMSCs osteogenic and adipogenic differentiation remained unaffected when cultured in (HEP/COL) multilayers in the presence of IFN-γ. We measured the immunomodulatory activity of hMSCs by measuring the level of indoleamine 2,3-dioxygenase (IDO) expression. IDO expression was higher on (HEP/COL) multilayers treated with IFN-γ. Lastly, we evaluated the suppression of peripheral blood mononuclear cell (PBMC) proliferation when co-cultured with hMSCs on (HEP/COL) multilayers with IFN-γ. hMSCs cultured in (HEP/COL) multilayers in the presence of soluble IFN-γ have a greater capacity to suppress PBMC proliferation. Altogether, (HEP/COL) multilayers with IFN-γ in culture medium provides a potent means of enhancing and sustaining immunomodulatory activity to control hMSCs immunomodulation.
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Affiliation(s)
- Mahsa Haseli
- Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA
| | - David A. Castilla-Casadiego
- Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA
- Mcketta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Luis Pinzon-Herrera
- Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA
| | - Alexander Hillsley
- Mcketta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Katherine A. Miranda-Munoz
- Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701, USA
| | - Srikanth Sivaraman
- Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701, USA
| | - Adrianne M. Rosales
- Mcketta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Raj R. Rao
- Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701, USA
| | - Jorge Almodovar
- Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA
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49
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Khamees N. The impact of media supplement on the viability, proliferation, and differentiation potential of bone marrow-derived mesenchymal stem cells. MUSTANSIRIYA MEDICAL JOURNAL 2022. [DOI: 10.4103/mj.mj_49_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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50
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Semenova E, Grudniak MP, Bocian K, Chroscinska-Krawczyk M, Trochonowicz M, Stepaniec IM, Murzyn M, Szablowska-Gadomska I, Boruczkowski D, Oldak T, Machaj EK. Banking of AT-MSC and its Influence on Their Application to Clinical Procedures. Front Bioeng Biotechnol 2021; 9:773123. [PMID: 34917599 PMCID: PMC8670380 DOI: 10.3389/fbioe.2021.773123] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 11/11/2021] [Indexed: 01/09/2023] Open
Abstract
Processing of MSCs to obtain a therapeutic product consists of two main steps: 1) the in vitro expansion of the cells until an appropriate number of them is obtained, and 2) freezing and storage of the expanded cells. The last step is critical and must be optimized so that after thawing the cells retain all their physiological properties including the secretory function. In this paper, we evaluated physiological parameters of AT-MSC's after a full cycle of their processing, particularly freezing and storing at the liquid nitrogen vapor temperature. Based on the recovered proliferative and secretory capacities of the thawed cells, we have designed the optimal technique for processing of MSCs for clinical applications. In our work, we tried to select the best DMSO-based cryoprotectant mixture on the base of post thawing fully retain their properties. We have demonstrated the effectiveness of the use of DMSO in various configurations of the constituent cryoprotective fluids. We have also shown that AT-MSCs that show control levels in most standard tests (viability, shape, culture behaviour, and proliferative properties) after thawing, may show transient variations in some important physiological properties, such as the level of secreted growth factors. Obtained results let us to indicate how to optimize the AT-MSC preparation process for clinical applications. We suggest that before their clinical application the cells should be cultured for at least one passage to recover their physiological stability and thus assure their optimal therapeutic potential.
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Affiliation(s)
| | | | - Katarzyna Bocian
- Polish Stem Cell Bank, FamiCord Group, Warsaw, Poland.,Department of Immunology, Faculty of Biology, University of Warsaw, Warsaw, Poland
| | | | | | | | - Magdalena Murzyn
- Polish Stem Cell Bank, FamiCord Group, Warsaw, Poland.,Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
| | | | | | - Tomasz Oldak
- Polish Stem Cell Bank, FamiCord Group, Warsaw, Poland
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