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Li L, He Y, Zhao J, Yin H, Feng X, Fan X, Wu W, Lu Q. Mesenchymal Stromal Cell-Based Therapy: A Promising Approach for Autoimmune Diseases. Clin Rev Allergy Immunol 2025; 68:21. [PMID: 39982546 DOI: 10.1007/s12016-025-09030-9] [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] [Accepted: 02/04/2025] [Indexed: 02/22/2025]
Abstract
Autoimmune diseases are characterized by immune dysregulation, resulting in aberrant reactivity of T cells and antibodies to self-antigens, leading to various patterns of inflammation and organ dysfunction. However, current therapeutic agents exhibit broad-spectrum activity and lack disease-specific selectivity, leading to enduring adverse effects, notably severe infections, and malignancies, and patients often fail to achieve the intended clinical goals. Mesenchymal stromal cells (MSCs) are multipotent stromal cells that can be easily derived from various tissues, such as adipose tissue, umbilical cords, Wharton's jelly, placenta, and dental tissues. MSCs offer advantages due to their immunomodulatory and anti-inflammatory abilities, low immunogenicity, and a high capacity for proliferation and multipotent differentiation, making them excellent candidates for cell-based treatment in autoimmune disorders. This review will cover preclinical studies and clinical trials involving MSCs in autoimmune diseases, as well as the primary challenges associated with the clinical application of MSC therapies and strategies for maximizing their therapeutic potential.
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Affiliation(s)
- Liming Li
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Yong He
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
| | - Junpeng Zhao
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
- Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China
| | - Huiqi Yin
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Xiwei Feng
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Xinyu Fan
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Wei Wu
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Qianjin Lu
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China.
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Dutra Alves NS, Reigado GR, Santos M, Caldeira IDS, Hernandes HDS, Freitas-Marchi BL, Zhivov E, Chambergo FS, Nunes VA. Advances in regenerative medicine-based approaches for skin regeneration and rejuvenation. Front Bioeng Biotechnol 2025; 13:1527854. [PMID: 40013305 PMCID: PMC11861087 DOI: 10.3389/fbioe.2025.1527854] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 01/20/2025] [Indexed: 02/28/2025] Open
Abstract
Significant progress has been made in regenerative medicine for skin repair and rejuvenation. This review examines core technologies including stem cell therapy, bioengineered skin substitutes, platelet-rich plasma (PRP), exosome-based therapies, and gene editing techniques like CRISPR. These methods hold promise for treating a range of conditions, from chronic wounds and burns to age-related skin changes and genetic disorders. Challenges remain in optimizing these therapies for broader accessibility and ensuring long-term safety and efficacy.
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Affiliation(s)
- Nathalia Silva Dutra Alves
- Laboratory of Skin Physiology and Tissue Bioengineering, School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil
| | - Gustavo Roncoli Reigado
- Laboratory of Skin Physiology and Tissue Bioengineering, School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil
| | - Mayara Santos
- Laboratory of Skin Physiology and Tissue Bioengineering, School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil
| | - Izabela Daniel Sardinha Caldeira
- Laboratory of Skin Physiology and Tissue Bioengineering, School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil
| | - Henrique dos Santos Hernandes
- Laboratory of Proteins and Biotechnology, School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil
| | | | - Elina Zhivov
- Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller Medical School, Miami, FL, United States
| | - Felipe Santiago Chambergo
- Laboratory of Proteins and Biotechnology, School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil
| | - Viviane Abreu Nunes
- Laboratory of Skin Physiology and Tissue Bioengineering, School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil
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Song M, Lim KM, Song K, Kang GH, Kim SJ, Lee Y, Yu S, Jeong KH, Cho SG. Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor- β1-Enriched Small-Sized Extracellular Vesicles. Int J Stem Cells 2024; 17:407-417. [PMID: 39396918 PMCID: PMC11612221 DOI: 10.15283/ijsc24089] [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: 07/29/2024] [Revised: 08/13/2024] [Accepted: 09/03/2024] [Indexed: 10/15/2024] Open
Abstract
Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton's jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJ-MSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.
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Affiliation(s)
- Myeongjin Song
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
- R&D Team, StemExOne Co., Ltd., Seoul, Korea
| | - Kyung Min Lim
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
- R&D Team, StemExOne Co., Ltd., Seoul, Korea
| | - Kwonwoo Song
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
- R&D Team, StemExOne Co., Ltd., Seoul, Korea
| | - Geun-Ho Kang
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
- R&D Team, StemExOne Co., Ltd., Seoul, Korea
| | - Se Jong Kim
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
- R&D Team, StemExOne Co., Ltd., Seoul, Korea
| | - Youngseo Lee
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
| | - Sujin Yu
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
| | - Ki-Heon Jeong
- Department of Dermatology, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
- R&D Team, StemExOne Co., Ltd., Seoul, Korea
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FAGOONEE S, ZANNETTI A, BUSSOLATI B. Adipose tissue-derived stem cells: a potent tool in regenerative medicine? MINERVA BIOTECHNOLOGY AND BIOMOLECULAR RESEARCH 2024; 36. [DOI: 10.23736/s2724-542x.24.03205-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/10/2025]
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Zeng L, Yang K, Yu G, Chen J, Long Z, Xiang W, Liu S, Zheng Y, Yan Y, Hao M, Sun L. Efficacy and safety of culture-expanded mesenchymal stromal cell therapy in the treatment of 4 types of inflammatory arthritis: A systematic review and meta-analysis of 36 randomized controlled trials. Semin Arthritis Rheum 2024; 68:152498. [PMID: 38970896 DOI: 10.1016/j.semarthrit.2024.152498] [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: 03/22/2024] [Revised: 05/09/2024] [Accepted: 05/29/2024] [Indexed: 07/08/2024]
Abstract
OBJECTIVE This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis. METHODS Two researchers conducted a comprehensive search of Chinese and English databases from their inception until July 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. RESULTS A total of 36 relevant RCTs, involving 2,076 participants, were ultimately included in this study. These RCTs encompassed four types of inflammatory arthritis, namely rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic sclerosis (SSc). The results demonstrated that MSC therapy exhibited improvements in the Visual Analog Scale (VAS) for pain in OA patients (bone marrow: SMD=-0.95, 95 % CI: -1.55 to -0.36, P = 0.002; umbilical cord: SMD=-2.03, 95 % CI: -2.99 to -1.07, P < 0.0001; adipose tissue: SMD=-1.26, 95 % CI: -1.99 to -0.52, P = 0.0009). Specifically, MSCs sourced from adipose tissue showed enhancements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (P = 0.0001), WOMAC physical function (P = 0.001), and total WOMAC scores (P = 0.0003). As for MSC therapy in RA, AS, and SSc, the current systematic review suggests a potential therapeutic effect of MSCs on these inflammatory arthritic conditions. Safety assessments indicated that MSC therapy did not increase the incidence of adverse events. CONCLUSION MSCs have the potential to alleviate joint pain and improve joint function in patients with inflammatory arthritis. Moreover, MSC therapy appears to be relatively safe and could be considered as a viable alternative treatment option for inflammatory arthritis.
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Affiliation(s)
- Liuting Zeng
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.
| | - Kailin Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China; Psychosomatic laboratory, Department of Psychiatry, Daqing Hospital of Traditional Chinese Medicine, Daqing, China.
| | - Ganpeng Yu
- People's Hospital of Ningxiang City, Ningxiang, China
| | - Junpeng Chen
- Psychosomatic laboratory, Department of Psychiatry, Daqing Hospital of Traditional Chinese Medicine, Daqing, China; Department of Physiology, School of Medicine, University of Louisville, Kentucky, USA; Tong Jiecheng Studio, Hunan University of Science and Technology, Xiangtan, China.
| | - Zhiyong Long
- Department of Physical Medicine and Rehabilitation, The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou, China
| | - Wang Xiang
- The First People's Hospital of Changde City, Changde, China
| | - Shuman Liu
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China
| | - Yaru Zheng
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China
| | - Yexing Yan
- Psychosomatic laboratory, Department of Psychiatry, Daqing Hospital of Traditional Chinese Medicine, Daqing, China
| | - Moujia Hao
- Psychosomatic laboratory, Department of Psychiatry, Daqing Hospital of Traditional Chinese Medicine, Daqing, China
| | - Lingyun Sun
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China; Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
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Yu HR, Huang HC, Chen IL, Li SC. Exosomes Secreted by Wharton's Jelly-Derived Mesenchymal Stem Cells Promote the Ability of Cell Proliferation and Migration for Keratinocyte. Int J Mol Sci 2024; 25:4758. [PMID: 38731977 PMCID: PMC11084911 DOI: 10.3390/ijms25094758] [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: 03/10/2024] [Revised: 04/23/2024] [Accepted: 04/24/2024] [Indexed: 05/13/2024] Open
Abstract
Mesenchymal stem cells (MSCs) isolated from Wharton's jelly (WJ-MSCs) and adipose tissue (AD-MSCs) are alternative sources for bone marrow-derived MSCs. Owing to their multiple functions in angiogenesis, immune modulation, proliferation, migration, and nerve regeneration, MSC-derived exosomes can be applied in "cell-free cell therapy". Here, we investigated the functional protein components between the exosomes from WJ-MSCs and AD-MSCs to explain their distinct functions. Proteins of WJ-MSC and AD-MSC exosomes were collected and compared based on iTRAQ gel-free proteomics data. Results: In total, 1695 proteins were detected in exosomes. Of these, 315 were more abundant (>1.25-fold) in AD-MSC exosomes and 362 kept higher levels in WJ-MSC exosomes, including fibrinogen proteins. Pathway enrichment analysis suggested that WJ-MSC exosomes had higher potential for wound healing than AD-MSC exosomes. Therefore, we treated keratinocyte cells with exosomes and the recombinant protein of fibrinogen beta chain (FGB). It turned out that WJ-MSC exosomes better promoted keratinocyte growth and migration than AD-MSC exosomes. In addition, FGB treatment had similar results to WJ-MSC exosomes. The fact that WJ-MSC exosomes promoted keratinocyte growth and migration better than AD-MSC exosomes can be explained by their higher FGB abundance. Exploring the various components of AD-MSC and WJ-MSC exosomes can aid in their different clinical applications.
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Affiliation(s)
- Hong-Ren Yu
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (H.-R.Y.); (H.-C.H.); (I.-L.C.)
| | - Hsin-Chun Huang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (H.-R.Y.); (H.-C.H.); (I.-L.C.)
| | - I-Lun Chen
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (H.-R.Y.); (H.-C.H.); (I.-L.C.)
| | - Sung-Chou Li
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan
- Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821004, Taiwan
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Sionov RV, Ahdut-HaCohen R. A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome. Biomedicines 2023; 11:2558. [PMID: 37761001 PMCID: PMC10527322 DOI: 10.3390/biomedicines11092558] [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: 08/15/2023] [Revised: 09/06/2023] [Accepted: 09/14/2023] [Indexed: 09/29/2023] Open
Abstract
Type 1 Diabetes (T1D) is a chronic autoimmune disease characterized by a gradual destruction of insulin-producing β-cells in the endocrine pancreas due to innate and specific immune responses, leading to impaired glucose homeostasis. T1D patients usually require regular insulin injections after meals to maintain normal serum glucose levels. In severe cases, pancreas or Langerhans islet transplantation can assist in reaching a sufficient β-mass to normalize glucose homeostasis. The latter procedure is limited because of low donor availability, high islet loss, and immune rejection. There is still a need to develop new technologies to improve islet survival and implantation and to keep the islets functional. Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells with high plasticity that can support human pancreatic islet function both in vitro and in vivo and islet co-transplantation with MSCs is more effective than islet transplantation alone in attenuating diabetes progression. The beneficial effect of MSCs on islet function is due to a combined effect on angiogenesis, suppression of immune responses, and secretion of growth factors essential for islet survival and function. In this review, various aspects of MSCs related to islet function and diabetes are described.
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Affiliation(s)
- Ronit Vogt Sionov
- The Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
| | - Ronit Ahdut-HaCohen
- Department of Medical Neurobiology, Institute of Medical Research, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel;
- Department of Science, The David Yellin Academic College of Education, Jerusalem 9103501, Israel
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Jensen NC, Robins J, Snyder AM, Harris R, Ferris LK, Johnson L. Psoriasis in the transplant population. Arch Dermatol Res 2023; 315:1109-1128. [PMID: 36459192 PMCID: PMC11199078 DOI: 10.1007/s00403-022-02487-0] [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: 04/25/2022] [Revised: 10/25/2022] [Accepted: 11/17/2022] [Indexed: 12/04/2022]
Abstract
Solid organ and stem cell transplants are increasingly common, and dermatologists will more frequently encounter and need to manage common skin diseases, such as psoriasis, in transplant patients. This review explores psoriasis remission and occurrence in recipients of solid organ and stem cell transplants. Hematopoietic and mesenchymal stem cell transplants may show potential for treating psoriasis in patients with leukemia or who have other medical conditions requiring stem cell transplant. The effects of solid organ transplant are less clear, partly due to limitations in the breadth of the literature. De novo psoriasis has been reported in recipients of solid organ transplants, but the reasons for this development have yet to be fully understood. Overall, the literature on this subject is limited to primarily case reports. Feasibility of studies on the subject may be a considerable barrier to further research assessing the use of transplant for treating psoriasis, but there is potential benefit from transplant for psoriasis patients. This subject should receive further exploration to fully understand these benefits.
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Affiliation(s)
| | - Jacob Robins
- Department of Dermatology, University of Utah, 30 North 1900 East, 4A330, Salt Lake City, UT, 84132, USA
| | - Ashley M Snyder
- Department of Dermatology, University of Utah, 30 North 1900 East, 4A330, Salt Lake City, UT, 84132, USA
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
| | | | - Laura Korb Ferris
- Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Luke Johnson
- Department of Dermatology, University of Utah, 30 North 1900 East, 4A330, Salt Lake City, UT, 84132, USA.
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Lei MJ, Bai F, Zhang QY, Yang QQ, Tian Z. Total Glucosides of Paeony Regulate Immune Imbalance Mediated by Dermal Mesenchymal Stem Cells in Psoriasis Mice. Chin J Integr Med 2023; 29:517-525. [PMID: 37222920 DOI: 10.1007/s11655-023-3737-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2023] [Indexed: 05/25/2023]
Abstract
OBJECTIVE To investigate the therapeutic effects of total glucosides of paeony (TGP) on psoriasis based on the immunomodulatory effect of dermal mesenchymal stem cells (DMSCs). METHODS A total of 30 male BALB/c mice were divided into 6 groups (n=5 in each) by a random number table method, including control, psoriasis model (model, 5% imiquimod cream 42 mg/d), low-, medium- and high-dose TGP (50, 100, and 200 mg/kg, L, M-, and H-TGP, respectively), and positive control group (2.5 mg/kg acitretin). After 14 days of continuous administration, the skin's histopathological changes, apoptosis, secretion of inflammatory cytokines, and proportion of regulatory T cells (Treg) and T helper cell 17 (Th17) were evaluated using hematoxylin-eosin (HE) staining, TdT-mediated dUTP nick end labeling staining, enzyme-linked immunosorbent assay, and flow cytometry, respectively. DMSCs were further isolated from the skin tissues of normal and psoriatic mice, and the cell morphology, phenotype, and cycle were observed. Furthermore, TGP was used to treat psoriatic DMSCs to analyze the effects on the DMSCs immune regulation. RESULTS TGP alleviated skin pathological injury, reduced epidermis layer thickness, inhibited apoptosis, and regulated the secretion of inflammatory cytokines and the proportion of Treg and Th17 in the skin tissues of psoriatic mice (P<0.05 or P<0.01). There was no significant difference in cell morphology and phenotype between control and psoriatic DMSCs (P>0.05), however, more psoriatic DMSCs remained in G0/G1 phase compared with the normal DMSCs (P<0.01). TGP treatment of psoriatic DMSCs significantly increased cell viability, decreased apoptosis, relieved inflammatory response, and inhibited the expression of toll-like receptor 4 and P65 (P<0.05 or P<0.01). CONCLUSION TGP may exert a good therapeutic effect on psoriasis by regulating the immune imbalance of DMSCs.
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Affiliation(s)
- Ming-Jun Lei
- Department of Dermatology, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, 050011, China
| | - Fan Bai
- Department of Dermatology, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, 050011, China
| | - Qing-Yun Zhang
- Department of Dermatology, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, 050011, China
| | - Qing-Qing Yang
- Department of Dermatology, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, 050011, China
| | - Zan Tian
- Department of Dermatology, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, 050011, China.
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Paganelli R, Paganelli A, Pawelec G, Di Iorio A. Natural IgG antibodies to β amyloid are decreased in patients with Parkinson's disease. Immun Ageing 2023; 20:13. [PMID: 36906630 PMCID: PMC10007830 DOI: 10.1186/s12979-023-00336-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 03/03/2023] [Indexed: 03/13/2023]
Abstract
Natural antibodies (nAbs) against aggregation-prone proteins have been found in healthy normal subjects. These proteins likely have a pathogenetic role in neurodegenerative diseases of ageing. They include the amyloid β (Aβ) protein which may play an important role in Alzheimer's dementia (AD), and α-synuclein, a major determinant of Parkinson's disease (PD). We measured nAbs to Aβ in a group of Italian patients with AD, vascular dementia, non-demented PD patients and healthy elderly controls. We found that Aβ antibody levels in AD were similar to age- and sex-matched controls, but contrary to our expectations, they were significantly reduced in PD. This may identify patients that could be more prone to amyloid aggregation.
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Affiliation(s)
- Roberto Paganelli
- Department of Medicine and Sciences of Aging, University "G. D'Annunzio", Chieti, Italy. .,Saint Camillus International University of Health and Medical Sciences, Rome, Italy. .,UniCamillus International Medical School, Via Di Sant'Alessandro, 8 - 00131, Rome, Italy.
| | - Alessia Paganelli
- Department of Biological, Metabolic and Neurological Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Graham Pawelec
- Department of Immunology, University of Tübingen, Tübingen, Germany.,Health Sciences North Research Institute, Sudbury, ON, Canada
| | - Angelo Di Iorio
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio", Chieti, Italy
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Yang J, Xiao M, Ma K, Li H, Ran M, Yang S, Yang Y, Fu X, Yang S. Therapeutic effects of mesenchymal stem cells and their derivatives in common skin inflammatory diseases: Atopic dermatitis and psoriasis. Front Immunol 2023; 14:1092668. [PMID: 36891306 PMCID: PMC9986293 DOI: 10.3389/fimmu.2023.1092668] [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: 11/08/2022] [Accepted: 01/31/2023] [Indexed: 02/22/2023] Open
Abstract
Chronic skin inflammatory diseases including atopic dermatitis (AD) and psoriasis have been considered uncontrolled inflammatory responses, which have usually troubled patients around the world. Moreover, the recent method to treat AD and psoriasis has been based on the inhibition, not regulation, of the abnormal inflammatory response, which can induce a number of side effects and drug resistance in long-term treatment. Mesenchymal stem/stromal cells (MSCs) and their derivatives have been widely used in immune diseases based on their regeneration, differentiation, and immunomodulation with few adverse effects, which makes MSCs a promising treatment for chronic skin inflammatory diseases. As a result, in this review, we aim to systematically discuss the therapeutic effects of various resources of MSCs, the application of preconditioning MSCs and engineering extracellular vesicles (EVs) in AD and psoriasis, and the clinical evaluation of the administration of MSCs and their derivatives, which can provide a comprehensive vision for the application of MSCs and their derivatives in future research and clinical treatment.
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Affiliation(s)
- Jie Yang
- Department of Dermatology, 4th Medical Centre, PLA General Hospital, Beijing, China.,Research Centre for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, China
| | - Minglu Xiao
- Department of Dermatology, 4th Medical Centre, PLA General Hospital, Beijing, China.,Research Centre for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, China
| | - Kui Ma
- Research Centre for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, China
| | - Hongyu Li
- Department of Dermatology, 4th Medical Centre, PLA General Hospital, Beijing, China.,Research Centre for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, China.,Tianjin Medical University, Tianjin, China
| | - Mingzi Ran
- Research Centre for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, China
| | - Shuxu Yang
- Department of Dermatology, 4th Medical Centre, PLA General Hospital, Beijing, China.,Research Centre for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, China
| | - Yuguang Yang
- Department of Dermatology, 4th Medical Centre, PLA General Hospital, Beijing, China
| | - Xiaobing Fu
- Research Centre for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, China
| | - Siming Yang
- Department of Dermatology, 4th Medical Centre, PLA General Hospital, Beijing, China.,Research Centre for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, China
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12
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Mesenchymal Stem Cells and Psoriasis: Systematic Review. Int J Mol Sci 2022; 23:ijms232315080. [PMID: 36499401 PMCID: PMC9740222 DOI: 10.3390/ijms232315080] [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: 10/04/2022] [Revised: 11/21/2022] [Accepted: 11/29/2022] [Indexed: 12/02/2022] Open
Abstract
Mesenchymal Stem Cells (MSCs) are multipotent non-hematopoietic stromal cells found in different body tissues such as bone marrow, adipose tissue, periosteum, Wharton's jelly, umbilical cord, blood, placenta, amniotic fluid, and skin. The biological behavior of MSCs depends mainly on their interaction with the microenvironment in which they are found, whose quality deeply influences the regenerative and immunomodulatory properties of these cells. Several studies confirm the interaction between MSCs and inflammatory microenvironment in the pathogenesis of psoriasis, designating MSCs as an important factor driving psoriasis development. This review aims to describe the most recent evidence on how the inflammatory microenvironment that characterizes psoriasis influences the homeostasis of MSCs and how they can be used to treat the disease.
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13
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Ahuja A, Tyagi PK, Kumar M, Sharma N, Prakash S, Radha, Chandran D, Dhumal S, Rais N, Singh S, Dey A, Senapathy M, Saleena LAK, Shanavas A, Mohankumar P, Rajalingam S, Murugesan Y, Vishvanathan M, Sathyaseelan SK, Viswanathan S, Kumar KK, Natta S, Mekhemar M. Botanicals and Oral Stem Cell Mediated Regeneration: A Paradigm Shift from Artificial to Biological Replacement. Cells 2022; 11:2792. [PMID: 36139367 PMCID: PMC9496740 DOI: 10.3390/cells11182792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/03/2022] [Accepted: 09/04/2022] [Indexed: 11/23/2022] Open
Abstract
Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells. The oral cavity is reported to be a rich source of multiple types of oral stem cells, including the dental pulp, mucosal soft tissues, periodontal ligament, and apical papilla. Oral stem cells were useful for both the regeneration of soft tissue components in the dental pulp and mineralized structure regeneration, such as bone or dentin, and can be a viable substitute for traditionally used bone marrow stem cells. In recent years, several studies have reported that plant extracts or compounds promoted the proliferation, differentiation, and survival of different oral stem cells. This review is carried out by following the PRISMA guidelines and focusing mainly on the effects of bioactive compounds on oral stem cell-mediated dental, bone, and neural regeneration. It is observed that in recent years studies were mainly focused on the utilization of oral stem cell-mediated regeneration of bone or dental mesenchymal cells, however, the utility of bioactive compounds on oral stem cell-mediated regeneration requires additional assessment beyond in vitro and in vivo studies, and requires more randomized clinical trials and case studies.
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Affiliation(s)
- Anami Ahuja
- Department of Biotechnology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow 226031, India
- Department of Biotechnology, Meerut Institute of Engineering and Technology, Meerut 250005, India
| | - Pankaj Kumar Tyagi
- Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida 201306, India
| | - Manoj Kumar
- Chemical and Biochemical Processing Division, ICAR–Central Institute for Research on Cotton Technology, Mumbai 400019, India
| | - Naveen Sharma
- Division of Biomedical Informatics, Indian Council of Medical Research, New Delhi 110029, India
| | - Suraj Prakash
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Radha
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sci-ences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Sangram Dhumal
- Division of Horticulture, RCSM College of Agriculture, Kolhapur 416004, India
| | - Nadeem Rais
- Department of Pharmacy, Bhagwant University, Ajmer 305004, India
| | - Surinder Singh
- Dr. S. S. Bhatnagar University Institute of Chemical Engineering and Technology, Panjab University, Chandigarh 160014, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata 700073, India
| | - Marisennayya Senapathy
- Department of Rural Development and Agricultural Extension, College of Agriculture, Wolaita Sodo University, Wolaita Sodo P.O. Box 138, Ethiopia
| | - Lejaniya Abdul Kalam Saleena
- Department of Food Science and Nutrition, Faculty of Applied Sciences, UCSI University, Kuala Lampur 56000, Malaysia
| | - Arjun Shanavas
- Division of Medicine, Indian Veterinary Research Institute, Bareilly 243122, India
| | - Pran Mohankumar
- School of Agriculture and Biosciences, Karunya Institute of Technology and Sciences, Coimbatore 641114, India
| | - Sureshkumar Rajalingam
- Department of Agronomy, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Yasodha Murugesan
- Department of Agronomy, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Marthandan Vishvanathan
- Department of Seed Science and Technology, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | | | - Sabareeshwari Viswanathan
- Department of Soil Science and Agricultural Chemistry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Keerthana Krishna Kumar
- Department of Soil Science and Agricultural Chemistry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Suman Natta
- ICAR—National Research Centre for Orchids, Pakyong 737106, India
| | - Mohamed Mekhemar
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Chris-tian-Albrecht’s University, 24105 Kiel, Germany
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14
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Human umbilical cord mesenchymal stem cells for psoriasis: a phase 1/2a, single-arm study. Signal Transduct Target Ther 2022; 7:263. [PMID: 35927231 PMCID: PMC9352692 DOI: 10.1038/s41392-022-01059-y] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 04/28/2022] [Accepted: 06/13/2022] [Indexed: 12/31/2022] Open
Abstract
Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4+ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4+ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4+ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957.
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15
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Human umbilical cord-derived mesenchymal stem cells ameliorate psoriasis-like dermatitis by suppressing IL-17-producing γδ T cells. Cell Tissue Res 2022; 388:549-563. [DOI: 10.1007/s00441-022-03616-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 03/10/2022] [Indexed: 12/14/2022]
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16
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Thakur V, Mahajan R. Novel Therapeutic Target(s) for Psoriatic Disease. Front Med (Lausanne) 2022; 9:712313. [PMID: 35265634 PMCID: PMC8898896 DOI: 10.3389/fmed.2022.712313] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 01/28/2022] [Indexed: 11/28/2022] Open
Abstract
Psoriasis and psoriatic arthritis, together known as psoriatic disease, is highly prevalent chronic relapsing inflammatory disease affecting skin, joints or both and is associated with several comorbidities such as cardiovascular, metabolic, psychiatric, renal disease etc. The etiopathogenesis of psoriasis is complex and mainly driven by aberrant immune response owing to the genetic susceptibility and various environmental factors such as trauma, infections and drugs. Recent advances in understanding molecular and cellular pathways have identified tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-23, IL-22 as major contributors in psoriasis pathogenesis. Advances in the knowledge of pathophysiology, the interaction of autoinflammation and clinical phenotypes have led to the development of highly effective targeted therapeutic agents which include TNF-α, IL-17, IL-23, IL-1 α/β or IL-36 inhibitors or receptor blockers, small molecule drugs like phosphodiesterase-4 inhibitors (apremilast), Janus kinase (JAK) inhibitors, retinoic acid receptor-related orphan receptor γt (RORγt) inhibitors. These novel drugs have promised the potential of improved disease control. In recent years, the transition from biologics to biosimilars especially with TNF-α inhibitors had significant impact on decreasing health care cost and increasing therapeutic options to the patients. However, selection of right treatment for an individual patient still remains challenging. Moreover, interplay between different epigenetic mechanisms such as the DNA methylation, chromatin modifications and noncoding RNA regulation has recently been started to be deciphered. Enzymes inhibitors involved in epigenetic pathways such as DNA methyltransferases and histone deacetylases demonstrated to restore normal epigenetic patterns in clinical settings and have provided the potential as novel therapeutic targets for psoriasis. In this review, we will discuss novel biologic agents and newer therapeutic approaches in treatment of psoriatic disease.
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17
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Paganelli A, Trubiani O, Diomede F, Pisciotta A, Paganelli R. Immunomodulating Profile of Dental Mesenchymal Stromal Cells: A Comprehensive Overview. FRONTIERS IN ORAL HEALTH 2022; 2:635055. [PMID: 35047993 PMCID: PMC8757776 DOI: 10.3389/froh.2021.635055] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 02/23/2021] [Indexed: 12/12/2022] Open
Abstract
Dental mesenchymal stromal cells (MSCs) are multipotent cells present in dental tissues, characterized by plastic adherence in culture and specific surface markers (CD105, CD73, CD90, STRO-1, CD106, and CD146), common to all other MSC subtypes. Dental pulp, periodontal ligament, apical papilla, human exfoliated deciduous teeth, alveolar bone, dental follicle, tooth germ, and gingiva are all different sources for isolation and expansion of MSCs. Dental MSCs have regenerative and immunomodulatory properties; they are scarcely immunogenic but actively modulate T cell reactivity. in vitro studies and animal models of autoimmune diseases have provided evidence for the suppressive effects of dental MSCs on peripheral blood mononuclear cell proliferation, clearance of apoptotic cells, and promotion of a shift in the Treg/Th17 cell ratio. Appropriately stimulated MSCs produce anti-inflammatory mediators, such as transforming growth factor-β (TGF-β), prostaglandin E2, and interleukin (IL)-10. A particular mechanism through which MSCs exert their immunomodulatory action is via the production of extracellular vesicles containing such anti-inflammatory mediators. Recent studies demonstrated MSC-mediated inhibitory effects both on monocytes and activated macrophages, promoting their polarization to an anti-inflammatory M2-phenotype. A growing number of trials focusing on MSCs to treat autoimmune and inflammatory conditions are ongoing, but very few use dental tissue as a cellular source. Recent results suggest that dental MSCs are a promising therapeutic tool for immune-mediated disorders. However, the exact mechanisms responsible for dental MSC-mediated immunosuppression remain to be clarified, and impairment of dental MSCs immunosuppressive function in inflammatory conditions and aging must be assessed before considering autologous MSCs or their secreted vesicles for therapeutic purposes.
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Affiliation(s)
- Alessia Paganelli
- PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy.,Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Oriana Trubiani
- Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" Chieti-Pescara, Chieti, Italy
| | - Francesca Diomede
- Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" Chieti-Pescara, Chieti, Italy
| | - Alessandra Pisciotta
- Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Roberto Paganelli
- Department of Medicine and Aging Sciences, University "G. D'Annunzio" Chieti-Pescara, Chieti, Italy.,YDA, Institute of Clinical Immunotherapy and Advanced Biological Treatments, Pescara, Italy
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18
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Foroutan T, Kassaee MZ, Salari M, Ahmady F, Molavi F, Moayer F. Magnetic Fe 3 O 4 @graphene oxide improves the therapeutic effects of embryonic stem cells on acute liver damage. Cell Prolif 2021; 54:e13126. [PMID: 34569673 PMCID: PMC8560617 DOI: 10.1111/cpr.13126] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 08/12/2021] [Accepted: 09/09/2021] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE Acute liver failure is usually associated with inflammation and oxidation of hepatocytes and has high mortality and resource costs. Mesenchymal stem cell (MSCs) has occasionally been reported to have no beneficial effect due to poor transplantation and the survival of implanted cells. Recent studies showed that embryonic stem cell (ESC)-derived MSCs are an alternative for regenerative medicine. On the other hand, graphene-based nanostructures have proven useful in biomedicine. In this study, we investigated whether magnetic graphene oxide (MGO) improved the effects of ESC-MSC conditioned medium (CM) on protecting hepatocytes and stimulating the regeneration of damaged liver cells. MATERIALS AND METHODS To provide a rat model of acute liver failure, male rats were injected intraperitoneally with carbon tetrachloride (CCl4 ). The rats were randomly divided into six groups, namely control, sham, CCl4 , ESC-MSC-CM, MGO and ESC-MSC-CM + MGO. In the experimental groups, the rats received, depending on the group, 2 ml/kg body weight CCl4 and either ESC-MSC-CM with 5 × 106 MSCs or 300 μg/kg body weight MGO or both. Symptoms of acute liver failure appeared 4 days after the injection. All groups were compared and analysed both histologically and biochemically 4 days after the injection. Finally, the results of ESC-MSC-CM and MSC-CM were compared. RESULTS The results indicated that the use of MGO enhanced the effect of ESC-MSC-CM on reducing necrosis, inflammation, aspartate transaminase, alanine aminotransferase and alkaline phosphatase in the CCl4 -induced liver failure of the rat model. Also, the expression of vascular endothelial growth factor and matrix metalloproteinase-9 (MMP-9) was significantly upregulated after treatment with MGO. Also, the results showed that the ESC-MSC-CM has more efficient effective compared to MSC-CM. CONCLUSION Magnetic graphene oxide improved the hepatoprotective effects of ESC-MSC-CM on acute liver damage, probably by suppressing necrosis, apoptosis and inflammation of hepatocytes.
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Affiliation(s)
- Tahereh Foroutan
- Department of Animal BiologyFaculty of Biological SciencesKharazmi UniversityTehranIran
| | | | - Mahdi Salari
- Department of Environmental Health EngineeringSchool of Public HealthHamadan University of Medical SciencesHamadanIran
| | - Fatemeh Ahmady
- Department of Animal BiologyFaculty of Biological SciencesKharazmi UniversityTehranIran
| | - Fatemeh Molavi
- Department of Animal BiologyFaculty of Biological SciencesKharazmi UniversityTehranIran
| | - Fariborz Moayer
- Faculty of Veterinary MedicineIslamic Azad UniversityKarajIran
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19
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Riedl J, Popp C, Eide C, Ebens C, Tolar J. Mesenchymal stromal cells in wound healing applications: role of the secretome, targeted delivery and impact on recessive dystrophic epidermolysis bullosa treatment. Cytotherapy 2021; 23:961-973. [PMID: 34376336 PMCID: PMC8569889 DOI: 10.1016/j.jcyt.2021.06.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/25/2021] [Accepted: 06/22/2021] [Indexed: 12/12/2022]
Abstract
Mesenchymal stromal cells (MSCs) are multi-potent stromal-derived cells capable of self-renewal that possess several advantageous properties for wound healing, making them of interest to the field of dermatology. Research has focused on characterizing the unique properties of MSCs, which broadly revolve around their regenerative and more recently discovered immunomodulatory capacities. Because of ease of harvesting and expansion, differentiation potential and low immunogenicity, MSCs have been leading candidates for tissue engineering and regenerative medicine applications for wound healing, yet results from clinical studies have been variable, and promising pre-clinical work has been difficult to reproduce. Therefore, the specific mechanisms of how MSCs influence the local microenvironment in distinct wound etiologies warrant further research. Of specific interest in MSC-mediated healing is harnessing the secretome, which is composed of components known to positively influence wound healing. Molecules released by the MSC secretome can promote re-epithelialization and angiogenesis while inhibiting fibrosis and microbial invasion. This review focuses on the therapeutic interest in MSCs with regard to wound healing applications, including burns and diabetic ulcers, with specific attention to the genetic skin disease recessive dystrophic epidermolysis bullosa. This review also compares various delivery methods to support skin regeneration in the hopes of combating the poor engraftment of MSCs after delivery, which is one of the major pitfalls in clinical studies utilizing MSCs.
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Affiliation(s)
- Julia Riedl
- Medical Scientist Training Program (MD/PhD), University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA
| | - Courtney Popp
- Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Cindy Eide
- Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Christen Ebens
- Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Jakub Tolar
- Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA.
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20
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Ahn H, Lee SY, Jung WJ, Pi J, Lee KH. Psoriasis treatment using minimally manipulated umbilical cord-derived mesenchymal stem cells: A case report. World J Clin Cases 2021; 9:6798-6803. [PMID: 34447827 PMCID: PMC8362539 DOI: 10.12998/wjcc.v9.i23.6798] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 05/24/2021] [Accepted: 07/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Psoriasis is a chronic autoimmune disease that usually manifests as a red scaly epidermis, induration, and hyperproliferation of basal keratinocytes. About 2% of the world’s population suffers from psoriasis but there are no clear therapeutics yet. Recently, mesenchymal stem cells (MSCs) have been regarded as a therapeutic alternative for autoimmune diseases, as they possess immunosuppressive effects without risks. Human umbilical cord-derived MSCs effectively regulate immune cells and are characterized by low immunogenicity, which has many advantages in treating immune diseases.
CASE SUMMARY The patient was a 47-year-old male, diagnosed with psoriasis in 1995. He had received various treatments for 25 years, but the psoriatic condition was not significantly improved. He was given three rounds of minimally manipulated umbilical cord-derived MSCs over 2 wk. The erythema gradually disappeared. Three months after the 1st round, all erythema completely disappeared, and the psoriasis did not recur.
CONCLUSION Minimally manipulated umbilical cord-derived MSC transplantation can potentially treat patients who suffer from psoriasis.
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Affiliation(s)
- Hyunjun Ahn
- bio Beauty&Health Company (bBHC)-Stem Cell Treatment and Research Institute (STRI), Seoul 04420, South Korea
- Department of Functional Genomics, University of Science and Technology KRIBB School, Deajeon 34113, South Korea
| | - Sang Yeon Lee
- bio Beauty&Health Company (bBHC)-Stem Cell Treatment and Research Institute (STRI), Seoul 04420, South Korea
| | - Won-Ju Jung
- Stem Cell Treatment, 97.7 B&H Clinic, Seoul 04420, South Korea
| | - Jia Pi
- bio Beauty&Health Company (bBHC)-Stem Cell Treatment and Research Institute (STRI), Seoul 04420, South Korea
| | - Kye-Ho Lee
- bio Beauty&Health Company (bBHC)-Stem Cell Treatment and Research Institute (STRI), Seoul 04420, South Korea
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21
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Kim D, Lee AE, Xu Q, Zhang Q, Le AD. Gingiva-Derived Mesenchymal Stem Cells: Potential Application in Tissue Engineering and Regenerative Medicine - A Comprehensive Review. Front Immunol 2021; 12:667221. [PMID: 33936109 PMCID: PMC8085523 DOI: 10.3389/fimmu.2021.667221] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 03/30/2021] [Indexed: 12/15/2022] Open
Abstract
A unique subpopulation of mesenchymal stem cells (MSCs) has been isolated and characterized from human gingival tissues (GMSCs). Similar to MSCs derived from other sources of tissues, e.g. bone marrow, adipose or umbilical cord, GMSCs also possess multipotent differentiation capacities and potent immunomodulatory effects on both innate and adaptive immune cells through the secretion of various types of bioactive factors with immunosuppressive and anti-inflammatory functions. Uniquely, GMSCs are highly proliferative and have the propensity to differentiate into neural cell lineages due to the neural crest-origin. These properties have endowed GMSCs with potent regenerative and therapeutic potentials in various preclinical models of human disorders, particularly, some inflammatory and autoimmune diseases, skin diseases, oral and maxillofacial disorders, and peripheral nerve injuries. All types of cells release extracellular vesicles (EVs), including exosomes, that play critical roles in cell-cell communication through their cargos containing a variety of bioactive molecules, such as proteins, nucleic acids, and lipids. Like EVs released by other sources of MSCs, GMSC-derived EVs have been shown to possess similar biological functions and therapeutic effects on several preclinical diseases models as GMSCs, thus representing a promising cell-free platform for regenerative therapy. Taken together, due to the easily accessibility and less morbidity of harvesting gingival tissues as well as the potent immunomodulatory and anti-inflammatory functions, GMSCs represent a unique source of MSCs of a neural crest-origin for potential application in tissue engineering and regenerative therapy.
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Affiliation(s)
- Dane Kim
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Alisa E Lee
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Qilin Xu
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Qunzhou Zhang
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Anh D Le
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States.,Center of Innovation & Precision Dentistry, School of Dental Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, United States.,Department of Oral & Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania, Philadelphia, PA, United States
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22
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Foroutan T, Ahmadi F, Moayer F, Khalvati S. Effects of intraperitoneal injection of magnetic graphene oxide on the improvement of acute liver injury induced by CCl 4. Biomater Res 2020; 24:14. [PMID: 32864158 PMCID: PMC7449094 DOI: 10.1186/s40824-020-00192-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 07/22/2020] [Indexed: 01/06/2023] Open
Abstract
Background Liver failure is usually associated with the inflammation and oxidation of hepatocytes. Due to their unique properties, graphene and graphene-based nanostructures such as magnetic graphene oxide (MGO) are useful in biomedicine and engineering. In this study, synthesized MGO was used to improve the liver failure induced by carbon tetrachloride (CCl4). The hepatoprotective effects of intraperitoneal injection of MGO on the rat model of CCl4-induced acute liver failure were investigated. Materials and methods In order to provide a rat model of acute liver failure, male rats were intraperitoneally injected with 2 ml/kg body weight CCl4. In the experimental groups, rats received 2 ml/kg CCl4 and 300 mg/kg MGO body weight simultaneously. Four days after injection, symptoms of acute liver failure appeared. The control, sham, CCl4, and CCl4 + MGO groups were compared and analyzed both histologically and biochemically. Results The results indicated that the MGO injection reduced all CCl4-induced liver failure such as necrosis, fibrosis, inflammation, aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in the experimental groups of the rat model of acute liver failure. Conclusion The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.
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Affiliation(s)
- Tahereh Foroutan
- Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Fatemeh Ahmadi
- Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Fariborze Moayer
- Department of Pathobiology, School of Veterinary Medicine, Karaj Branch, Islamic Azad University, Karaj, Iran
| | - Sahar Khalvati
- Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
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