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Zubair M, Abouelnazar FA, Iqbal MA, Pan J, Zheng X, Chen T, Shen W, Yin J, Yan Y, Liu P, Mao F, Chu Y. Mesenchymal stem cell-derived exosomes as a plausible immunomodulatory therapeutic tool for inflammatory diseases. Front Cell Dev Biol 2025; 13:1563427. [PMID: 40129569 PMCID: PMC11931156 DOI: 10.3389/fcell.2025.1563427] [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: 01/20/2025] [Accepted: 02/21/2025] [Indexed: 03/26/2025] Open
Abstract
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), especially, exosomes are considered to have diverse therapeutic effects for various significant diseases. MSC-derived exosomes (MSCex) offer substantial advantages over MSCs due to their long-term preservation, stability, absence of nuclei and fewer adverse effects such as infusion toxicity, thereby paving the way towards regenerative medicine and cell-free therapeutics. These exosomes harbor several cellular contents such as DNA, RNA, lipids, metabolites, and proteins, facilitating drug delivery and intercellular communication. MSCex have the ability to immunomodulate and trigger the anti-inflammatory process hence, playing a key role in alleviating inflammation and enhancing tissue regeneration. In this review, we addressed the anti-inflammatory effects of MSCex and the underlying immunomodulatory pathways. Moreover, we discussed the recent updates on MSCex in treating specific inflammatory diseases, including arthritis, inflammatory bowel disease, inflammatory eye diseases, and respiratory diseases such as asthma and acute respiratory distress syndrome (ARDS), as well as neurodegenerative and cardiac diseases. Finally, we highlighted the challenges in using MSCex as the successful therapeutic tool and discussed future perspectives.
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Affiliation(s)
- Muhammad Zubair
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
| | - Fatma A. Abouelnazar
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
- Faculty of Applied Health Sciences Technology, Pharos University, Alexandria, Egypt
| | | | - Jingyun Pan
- Department of Traditional Chinese Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
| | - Xuwen Zheng
- Department of Emergency, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Tao Chen
- Department of Gastroenterology, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Wenming Shen
- Department of Emergency, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Jinnan Yin
- Department of Emergency, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Yongmin Yan
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
| | - Pengjun Liu
- Department of Gastroenterology, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Fei Mao
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ying Chu
- Wujin Clinical College, Xuzhou Medical University, Changzhou, China
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
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2
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Cao F, Li Z, Ding W, Qv C, Zhao H. Exosomal miR-15a-5p from cardiomyocytes promotes myocardial fibrosis. Mol Cell Biochem 2025; 480:1701-1713. [PMID: 39110279 DOI: 10.1007/s11010-024-05080-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 07/25/2024] [Indexed: 02/21/2025]
Abstract
The emergence of myofibroblasts is a key step in myocardial fibrosis, but the trigger for the transformation of cardiac fibroblasts into myofibroblasts remains not entirely clear. Exosomes play a key role between cardiomyocytes and cardiac fibroblasts. Here, we not only investigated the relationship between exosomes derived from angiotensin (Ang)-II-treated cardiomyocytes and cardiac fibroblasts, the underlying mechanisms were also explored. Ang-II-treated C57 male mice and mouse cardiac fibroblasts were employed for in vivo and in vitro experiments, respectively. Transmission electron microscopy nanoparticle tracking analysis, and western blot of CD9, CD63, CD81 were performed to identify exosomes; QRT-PCR was performed to detect miR-15a-5p expression; luciferase reporter assay was employed to determine the interaction between miR-15a-5p and dyrk2; western blot was performed to examine the protein levels of fibrosis markers; Counting Kit-8 was performed to determine cell viability; HE and Masson staining were performed to assess the pathological changes of myocardial tissues. MiR-15a-5p expression was found up-regulated in serum of myocardial fibrosis patients, serum and myocardial tissues of Ang-II-treated mice, and Ang-II-treated cardiomyocytes. Mechanically, exosomes from Ang-II-treated cardiomyocytes shuttled miR-15a-5p to cardiac fibroblasts, where miR-15a-5p dephosphorylated NFAT by targeting dyrk2 to promote cell viability and elevated the protein levels of α-smooth muscle actin, collagen type 1 α1 and collagen type 3 α1, thus promoting myocardial fibrosis. This study identified a novel molecular target for anti-fibrotic therapeutic interventions.
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Affiliation(s)
- Feng Cao
- Department of Cardiology, Renmin Hospital of Wuhan University, NO.99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, China.
- Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, China.
- Hubei Key Laboratory of Cardiology, Wuhan, 430060, China.
| | - Zhe Li
- Department of Cardiology, Renmin Hospital of Wuhan University, NO.99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, China
- Hubei Key Laboratory of Cardiology, Wuhan, 430060, China
| | - Wenmao Ding
- Department of Cardiology, Renmin Hospital of Wuhan University, NO.99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, China
- Hubei Key Laboratory of Cardiology, Wuhan, 430060, China
| | - Chuan Qv
- Department of Cardiology, Renmin Hospital of Wuhan University, NO.99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, China
- Hubei Key Laboratory of Cardiology, Wuhan, 430060, China
| | - Hongyi Zhao
- Department of Cardiology, Renmin Hospital of Wuhan University, NO.99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, China
- Hubei Key Laboratory of Cardiology, Wuhan, 430060, China
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Pakdaman Kolour SS, Nematollahi S, Dehbozorgi M, Fattahi F, Movahed F, Esfandiari N, Kahrizi MS, Ghavamikia N, Hajiagha BS. Extracecellulr vesicles (EVs) microRNAs (miRNAs) derived from mesenchymal stem cells (MSCs) in osteoarthritis (OA); detailed role in pathogenesis and possible therapeutics. Heliyon 2025; 11:e42258. [PMID: 40007782 PMCID: PMC11850152 DOI: 10.1016/j.heliyon.2025.e42258] [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: 04/02/2024] [Revised: 01/23/2025] [Accepted: 01/23/2025] [Indexed: 02/27/2025] Open
Abstract
The primary cause of pain and disability in the world is osteoarthritis (OA), a common joint disease characterized by the primary pathological alteration in articular cartilage deterioration. The general outcome of treatment is not acceptable despite current interventions. Therefore, joint replacement surgery is frequently needed by patients with severe OA. Mesenchymal stem cells (MSCs) have become a practical treatment choice for preclinical and clinical OA palliation in recent years, mainly due to their unique immunomodulatory attributes. Further, attractive candidates for cell-free therapy for OA are MSC-derived extracecellulr vesicles (EVs) that convey bioactive molecules of the original cells, such as microRNAs. These EVs have been shown to significantly influence the regulation of various physiological activities of cells in the joint cavity. Dysregulated miRNAs upregulate the synthesis of enzymes that degrade cartilage, downregulate the expression of components in the cartilage matrix, promote the production of proinflammatory cytokines, induce programmed cell death in chondrocytes, inhibit the process of autophagy in chondrocytes, and participate in pathways related to pain. MiRNAs are also found in extracellular membranous vesicles (EVs), such as exosomes, and play a role in intercellular communication in osteoarthritic joints. Thus, the biosynthesis, chemical makeup, and mechanism of action of miRNAs-enriched EVs in OA are all thoroughly covered in this review. We additionally discussed how miRNA-enriched MSC-EVs might be used therapeutically to change intercellular interaction in OA.
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Affiliation(s)
| | - Saeide Nematollahi
- Department of Radiology, Kerman University of Paramedical Sciences, Kerman, Iran
| | | | | | - Fatemeh Movahed
- Department of Gynecology, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | - Nima Ghavamikia
- Cardiovascular Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahareh Salmanian Hajiagha
- Department of Cellular and Molecular Biology, Faculty of Basic Science, East Tehran Branch, Islamic Azad University, Tehran, Iran
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Tang A, Shu Q, Jia S, Lai Z, Tian J. Adipose Mesenchymal Stem Cell-Derived Exosomes as Nanocarriers for Treating Musculoskeletal Disorders. Int J Nanomedicine 2024; 19:13547-13562. [PMID: 39720215 PMCID: PMC11668248 DOI: 10.2147/ijn.s486622] [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: 07/11/2024] [Accepted: 11/22/2024] [Indexed: 12/26/2024] Open
Abstract
Musculoskeletal disorders are a series of diseases involving bone, muscle, cartilage, and tendon, mainly caused by chronic strain, degenerative changes, and structural damage due to trauma. The disorders limit the function of patients due to pain and significantly reduce their quality of life. In recent years, adipose-derived mesenchymal stem cells have been extensively applied in regeneration medicine research due to their particular abilities of self-renewal, differentiation, and targeted homing and are more easily accessed compared with other sources. The paracrine effect of ADSCs plays a crucial role in intercellular communication by releasing mass mediators, including cytokines and growth factors, particularly the exosomes they secrete. Not only do these exosomes possess low immunogenicity, low toxicity, and an enhanced ability to penetrate a bio-barrier, but they also inherit their parent cells' characteristics and carry various bioactive molecules to release to targeted cells, modulating their biological process. Meanwhile, these characteristics also make exosomes a natural nanocarrier capable of targeted drug delivery to specific sites, enhancing the bioavailability of drugs within the body and achieving precision therapy with fewer toxic side effects. Furthermore, the integration of exosomes with tissue engineering and chemical modification strategies can also significantly enhance their efficacy in facilitating tissue repair. However, the current research on ADSC-Exos for improving MSDs remains at an early stage and needs further exploration. Therefore, this review summarized the ADSC-Exo as a nanodrug carrier characteristics and mechanism in the treatment of fracture, osteoporosis, osteoarthritis, intervertebral disc degeneration, and tendon injury, which push forward the research progress of ADSC-Exo therapy for MSDs.
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Affiliation(s)
- Ao Tang
- Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China
- College of Sports Medicine, Wuhan Sports University, Wuhan, People’s Republic of China
| | - Qing Shu
- Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China
- College of Sports Medicine, Wuhan Sports University, Wuhan, People’s Republic of China
| | - Shaohui Jia
- College of Sports Medicine, Wuhan Sports University, Wuhan, People’s Republic of China
| | - Zhihao Lai
- Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Jun Tian
- Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China
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Kong Y, Wang Y, Yang Y, Hou Y, Yu J, Liu M, Xie S, Song Y. Intra-articular injection of exosomes derived from different stem cells in animal models of osteoarthritis: a systematic review and meta- analysis. J Orthop Surg Res 2024; 19:834. [PMID: 39696589 DOI: 10.1186/s13018-024-05227-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 11/01/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND In recent years, the increasing incidence of osteoarthritis (OA) has attracted widespread public attention; however, the available effective treatments are limited. As a result, new therapeutic approaches, including stem cell and exosome therapies, have been proposed and are gradually gaining popularity. Because exosomes are immunocompatible, there is thought to be more potential for their use in clinical settings. This study summarizes the efficacy of exosomes in the treatment of OA. METHODS In total, we conducted a comprehensive search of the PubMed, Web of Science, and Embase databases using medical subject headings terms to identify studies published from their inception until November 2023 that investigated the use of stem cell-derived exosomes in treating OA. We focused on specific outcomes including osteophyte score, chondrocyte count, pain level, qPCR and histological assessments such as the OARSI (Osteoarthritis research society international) score to measure cartilage degeneration. For data extraction, we used GetData Graph Digitizer to retrieve values from graphs, and the meta-analysis was conducted using RevMan 5.3 software. We chose mean difference (MD) as the primary effect measure since all included studies reported the same outcomes. Ultimately, 20 articles met the inclusion criteria and were included in the meta-analysis. RESULTS We evaluated 20 studies comprising a total of 400 subjects. Compared with control groups, the exosome-treated groups showed significantly improved histological outcomes, as measured by the OARSI score (n = 400; MD = -3.54; 95% CI = [-4.30, -2.79]; P < 0.00001; I2 = 98%). This indicates a marked reduction in cartilage degeneration and OA severity in the exosome-treated groups. Notably, exosome therapy was more effective when administered during the early stages of OA. Additionally, a once-weekly dosing schedule yielded better results compared to more frequent administrations. Of the three exosome isolation methods assessed, kit-based extraction demonstrated a trend toward superior therapeutic efficacy. CONCLUSIONS Exosome treatment improved OA compared to placebo treatment.
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Affiliation(s)
- Yajie Kong
- Department of Orthopedics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People's Republic of China
- Hebei Medical University National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
| | - Yuzhong Wang
- Department of Orthopedics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People's Republic of China
- Hebei Key Laboratory of Rare Disease, Shijiazhuang, 050000, Hebei Province, People's Republic of China
| | - Yujia Yang
- Hebei Medical University National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
| | - Yu Hou
- Hebei Medical University National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
| | - Jingjing Yu
- Hebei Medical University National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
| | - Meiling Liu
- Department of Orthopedics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People's Republic of China
- Hebei Medical University National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
| | - Siyi Xie
- Department of Orthopedics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People's Republic of China
- Hebei Medical University National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
- Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
| | - Yongzhou Song
- Department of Orthopedics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People's Republic of China.
- Hebei Key Laboratory of Rare Disease, Shijiazhuang, 050000, Hebei Province, People's Republic of China.
- Hebei Medical University National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China.
- Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China.
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Jones M, Jones E, Kouroupis D. The Use of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles in the Treatment of Osteoarthritis: Insights from Preclinical Studies. Bioengineering (Basel) 2024; 11:961. [PMID: 39451337 PMCID: PMC11504680 DOI: 10.3390/bioengineering11100961] [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: 08/21/2024] [Revised: 09/16/2024] [Accepted: 09/24/2024] [Indexed: 10/26/2024] Open
Abstract
Osteoarthritis (OA) is a prominent cause of disability, and has severe social and economic ramifications across the globe. The main driver of OA's pervasiveness is the fact that no current medical interventions exist to reverse or even attenuate the degeneration of cartilage within the articular joint. Crucial for cell-to-cell communication, extracellular vesicles (EVs) contribute to OA progression through the delivery of bioactive molecules in the inflammatory microenvironment. By repurposing this acellular means of signal transmission, therapeutic drugs may be administered to degenerated cartilage tissue in the hopes of encouraging regeneration. Positive outcomes are apparent in in vivo studies on this subject; however, for this therapy to prove itself in the clinical world, efforts towards standardizing the characterization, application, biological contents, and dosage are essential.
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Affiliation(s)
- Mitch Jones
- Department of Chemistry, Loughborough University, Loughborough LE11 3TU, UK;
| | - Elena Jones
- Leeds Institute of Rheumatic and Musculoskeletal Disease, University of Leeds, Leeds LS2 9JT, UK
| | - Dimitrios Kouroupis
- Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL 33146, USA
- Diabetes Research Institute & Cell Transplant Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
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7
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Amato L, De Rosa C, De Rosa V, Heydari Sheikhhossein H, Ariano A, Franco P, Nele V, Capaldo S, Di Guida G, Sepe F, Di Liello A, De Rosa G, Tuccillo C, Gambardella A, Ciardiello F, Morgillo F, Tirino V, Della Corte CM, Iommelli F, Vicidomini G. Immune-Cell-Derived Exosomes as a Potential Novel Tool to Investigate Immune Responsiveness in SCLC Patients: A Proof-of-Concept Study. Cancers (Basel) 2024; 16:3151. [PMID: 39335123 PMCID: PMC11430591 DOI: 10.3390/cancers16183151] [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: 07/08/2024] [Revised: 08/30/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
Small cell lung cancer (SCLC) is a highly invasive and rapidly proliferating lung tumor subtype. Most patients respond well to a combination of platinum-based chemotherapy and PD-1/PDL-1 inhibitors. Unfortunately, not all patients benefit from this treatment regimen, and few alternative therapies are available. In this scenario, the identification of new biomarkers and differential therapeutic strategies to improve tumor response becomes urgent. Here, we investigated the role of exosomes (EXs) released from the peripheral blood mononuclear cells (PBMCs) of SCLC patients in mediating the functional crosstalk between the immune system and tumors in response to treatments. In this study, we showed that PBMC-EXs from SCLC patients with different responses to chemoimmunotherapy showed different levels of immune (STING and MAVS) and EMT (Snail and c-Myc) markers. We demonstrated that PBMC-EXs derived from best responder (BR) patients were able to induce a significant increase in apoptosis in SCLC cell lines in vitro compared to PBMC-EXs derived from non-responder (NR) SCLC patients. PBMC-EXs were able to affect cell viability and modulate apoptotic markers, DNA damage and the replication stress pathway, as well as the occurrence of EMT. Our work provides proof of concept that PBMC-EXs can be used as a tool to study the crosstalk between cancer cells and immune cells and that PBMC-EXs exhibit an in vitro ability to promote cancer cell death and reduce tumor aggressiveness.
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Affiliation(s)
- Luisa Amato
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Caterina De Rosa
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Viviana De Rosa
- Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy; (V.D.R.); (F.I.)
| | - Hamid Heydari Sheikhhossein
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy;
- Villa Serena Foundation for Research, 65013 Città Sant’Angelo, Italy
| | - Annalisa Ariano
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Paola Franco
- Institute of Genetics and Biophysics Adriano Buzzati Traverso, National Research Council, 80131 Naples, Italy;
| | - Valeria Nele
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (V.N.); (G.D.R.)
| | - Sara Capaldo
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Gaetano Di Guida
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Filippo Sepe
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Alessandra Di Liello
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Giuseppe De Rosa
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (V.N.); (G.D.R.)
| | - Concetta Tuccillo
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Antonio Gambardella
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Fortunato Ciardiello
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Floriana Morgillo
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Virginia Tirino
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 81100 Caserta, Italy
| | - Carminia Maria Della Corte
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (A.A.); (S.C.); (G.D.G.); (F.S.); (A.D.L.); (C.T.); (A.G.); (F.C.); (F.M.)
| | - Francesca Iommelli
- Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy; (V.D.R.); (F.I.)
| | - Giovanni Vicidomini
- Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
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Karoichan A, Boucenna S, Tabrizian M. Therapeutics of the future: Navigating the pitfalls of extracellular vesicles research from an osteoarthritis perspective. J Extracell Vesicles 2024; 13:e12435. [PMID: 38943211 PMCID: PMC11213691 DOI: 10.1002/jev2.12435] [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: 01/22/2024] [Revised: 03/12/2024] [Accepted: 03/22/2024] [Indexed: 07/01/2024] Open
Abstract
Extracellular vesicles have gained wide momentum as potential therapeutics for osteoarthritis, a highly prevalent chronic disease that still lacks an approved treatment. The membrane-bound vesicles are secreted by all cells carrying different cargos that can serve as both disease biomarkers and disease modifiers. Nonetheless, despite a significant peak in research regarding EVs as OA therapeutics, clinical implementation seems distant. In addition to scalability and standardization challenges, researchers often omit to focus on and consider the proper tropism of the vesicles, the practicality and relevance of their source, their low native therapeutic efficacy, and whether they address the disease as a whole. These considerations are necessary to better understand EVs in a clinical light and have been comprehensively discussed and ultimately summarized in this review into a conceptualized framework termed the nanodiamond concept. Future perspectives are also discussed, and alternatives are presented to address some of the challenges and concerns.
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Affiliation(s)
- Antoine Karoichan
- Faculty of Dental Medicine and Oral Health SciencesMcGill UniversityMontrealQuebecCanada
| | - Sarah Boucenna
- Faculty of Dental Medicine and Oral Health SciencesMcGill UniversityMontrealQuebecCanada
| | - Maryam Tabrizian
- Faculty of Dental Medicine and Oral Health SciencesMcGill UniversityMontrealQuebecCanada
- Department of Biomedical EngineeringMcGill UniversityMontrealQuebecCanada
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9
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Ding Z, Greenberg ZF, Serafim MF, Ali S, Jamieson JC, Traktuev DO, March K, He M. Understanding molecular characteristics of extracellular vesicles derived from different types of mesenchymal stem cells for therapeutic translation. EXTRACELLULAR VESICLE 2024; 3:100034. [PMID: 38957857 PMCID: PMC11218754 DOI: 10.1016/j.vesic.2024.100034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
Abstract
Mesenchymal stem cells (MSCs) have been studied for decades as candidates for cellular therapy, and their secretome, including secreted extracellular vesicles (EVs), has been identified to contribute significantly to regenerative and reparative functions. Emerging evidence has suggested that MSC-EVs alone, could be used as therapeutics that emulate the biological function of MSCs. However, just as with MSCs, MSC-EVs have been shown to vary in composition, depending on the tissue source of the MSCs as well as the protocols employed in culturing the MSCs and obtaining the EVs. Therefore, the importance of careful choice of cell sources and culture environments is receiving increasing attention. Many factors contribute to the therapeutic potential of MSC-EVs, including the source tissue, isolation technique, and culturing conditions. This review illustrates the molecular landscape of EVs derived from different types of MSC cells along with culture strategies. A thorough analysis of publicly available omic datasets was performed to advance the precision understanding of MSC-EVs with unique tissue source-dependent molecular characteristics. The tissue-specific protein and miRNA-driven Reactome ontology analysis was used to reveal distinct patterns of top Reactome ontology pathways across adipose, bone marrow, and umbilical MSC-EVs. Moreover, a meta-analysis assisted by an AI technique was used to analyze the published literature, providing insights into the therapeutic translation of MSC-EVs based on their source tissues.
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Affiliation(s)
- Zuo Ding
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32611, USA
| | - Zachary F. Greenberg
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32611, USA
| | - Maria Fernanda Serafim
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32611, USA
| | - Samantha Ali
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32611, USA
| | - Julia C. Jamieson
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32611, USA
| | - Dmitry O. Traktuev
- UF Center for Regenerative Medicine, Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA
| | - Keith March
- UF Center for Regenerative Medicine, Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA
| | - Mei He
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32611, USA
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10
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Papadopoulos KS, Piperi C, Korkolopoulou P. Clinical Applications of Adipose-Derived Stem Cell (ADSC) Exosomes in Tissue Regeneration. Int J Mol Sci 2024; 25:5916. [PMID: 38892103 PMCID: PMC11172884 DOI: 10.3390/ijms25115916] [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: 04/29/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
Adipose-derived stem cells (ADSCs) are mesenchymal stem cells with a great potential for self-renewal and differentiation. Exosomes derived from ADSCs (ADSC-exos) can imitate their functions, carrying cargoes of bioactive molecules that may affect specific cellular targets and signaling processes. Recent evidence has shown that ADSC-exos can mediate tissue regeneration through the regulation of the inflammatory response, enhancement of cell proliferation, and induction of angiogenesis. At the same time, they may promote wound healing as well as the remodeling of the extracellular matrix. In combination with scaffolds, they present the future of cell-free therapies and promising adjuncts to reconstructive surgery with diverse tissue-specific functions and minimal adverse effects. In this review, we address the main characteristics and functional properties of ADSC-exos in tissue regeneration and explore their most recent clinical application in wound healing, musculoskeletal regeneration, dermatology, and plastic surgery as well as in tissue engineering.
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Affiliation(s)
- Konstantinos S. Papadopoulos
- Department of Plastic and Reconstructive Surgery, 401 General Military Hospital of Athens, 11525 Athens, Greece;
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Christina Piperi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street, 11527 Athens, Greece
| | - Penelope Korkolopoulou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
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11
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Huang H, Chen P, Feng X, Qian Y, Peng Z, Zhang T, Wang Q. Translational studies of exosomes in sports medicine - a mini-review. Front Immunol 2024; 14:1339669. [PMID: 38259444 PMCID: PMC10800726 DOI: 10.3389/fimmu.2023.1339669] [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: 11/16/2023] [Accepted: 12/18/2023] [Indexed: 01/24/2024] Open
Abstract
This review in sports medicine focuses on the critical role of exosomes in managing chronic conditions and enhancing athletic performance. Exosomes, small vesicles produced by various cells, are essential for cellular communication and transporting molecules like proteins and nucleic acids. Originating from the endoplasmic reticulum, they play a vital role in modulating inflammation and tissue repair. Their significance in sports medicine is increasingly recognized, particularly in healing athletic injuries, improving articular cartilage lesions, and osteoarthritic conditions by modulating cellular behavior and aiding tissue regeneration. Investigations also highlight their potential in boosting athletic performance, especially through myocytes-derived exosomes that may enhance adaptability to physical training. Emphasizing a multidisciplinary approach, this review underlines the need to thoroughly understand exosome biology, including their pathways and classifications, to fully exploit their therapeutic potential. It outlines future directions in sports medicine, focusing on personalized treatments, clinical evaluations, and embracing technological advancements. This research represents a frontier in using exosomes to improve athletes' health and performance capabilities.
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Affiliation(s)
- Haoqiang Huang
- Department of Orthopaedics, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, China
| | - Peng Chen
- Department of Sports Medicine, Peking University Shenzhen Hospital, Shenzhen, China
| | - Xinting Feng
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yinhua Qian
- Department of Orthopaedics, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, China
| | - Zhijian Peng
- Department of Orthopaedics, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, China
| | - Ting Zhang
- Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Qing Wang
- Department of Orthopaedics, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, China
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12
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Bertolino GM, Maumus M, Jorgensen C, Noël D. Therapeutic potential in rheumatic diseases of extracellular vesicles derived from mesenchymal stromal cells. Nat Rev Rheumatol 2023; 19:682-694. [PMID: 37666995 DOI: 10.1038/s41584-023-01010-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2023] [Indexed: 09/06/2023]
Abstract
The incidence of rheumatic diseases such as rheumatoid arthritis and osteoarthritis and injuries to articular cartilage that lead to osteochondral defects is predicted to rise as a result of population ageing and the increase in high-intensity physical activities among young and middle-aged people. Current treatments focus on the management of pain and joint functionality to improve the patient's quality of life, but curative strategies are greatly desired. In the past two decades, the therapeutic value of mesenchymal stromal cells (MSCs) has been evaluated because of their regenerative potential, which is mainly attributed to the secretion of paracrine factors. Many of these factors are enclosed in extracellular vesicles (EVs) that reproduce the main functions of parental cells. MSC-derived EVs have anti-inflammatory, anti-apoptotic as well as pro-regenerative activities. Research on EVs has gained considerable attention as they are a potential cell-free therapy with lower immunogenicity and easier management than whole cells. MSC-derived EVs can rescue the pathogenetic phenotypes of chondrocytes and exert a protective effect in animal models of rheumatic disease. To facilitate the therapeutic use of EVs, appropriate cell sources for the production of EVs with the desired biological effects in each disease should be identified. Production and isolation of EVs should be optimized, and pre-isolation and post-isolation modifications should be considered to maximize the disease-modifying potential of the EVs.
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Affiliation(s)
| | - Marie Maumus
- IRMB, University of Montpellier, INSERM, 34295, Montpellier, France
| | - Christian Jorgensen
- IRMB, University of Montpellier, INSERM, 34295, Montpellier, France.
- Clinical Immunology and Osteoarticular Disease Therapeutic Unit, Department of Rheumatology, CHU Montpellier, 34095, Montpellier, France.
| | - Danièle Noël
- IRMB, University of Montpellier, INSERM, 34295, Montpellier, France.
- Clinical Immunology and Osteoarticular Disease Therapeutic Unit, Department of Rheumatology, CHU Montpellier, 34095, Montpellier, France.
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13
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Davoodi Asl F, Sahraei SS, Kalhor N, Fazaeli H, Sheykhhasan M, Soleimani Moud S, Naserpour L, Sheikholeslami A. Promising effects of exosomes from menstrual blood-derived mesenchymal stem cells on endometriosis. Reprod Biol 2023; 23:100788. [PMID: 37542905 DOI: 10.1016/j.repbio.2023.100788] [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: 05/06/2023] [Revised: 06/26/2023] [Accepted: 07/14/2023] [Indexed: 08/07/2023]
Abstract
Endometriosis as a non-malignant gynecological disease leads to dysregulation of numerous cellular functions including apoptosis, angiogenesis, migration, proliferation, and inflammation. Accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. According to the fact that the therapeutic benefits of mesenchymal stem cells are provided through paracrine functions, we used exosomes from menstrual blood-derived stem cells (MenSCs) for treating endometriotic stem cells to inhibit their lesion formation tendency. Menstrual blood samples from healthy and endometriosis women were collected. Isolated MenSCs by the density-gradient centrifugation method were characterized by flow cytometry. Secreted exosomes were isolated from healthy MenSCs (NE-MenSCs) and used to treat endometriotic cells (E-MenSCs). 72 h after treatment, different mechanisms and pathways including inflammation, proliferation, apoptosis, migration, and angiogenesis were analyzed using Real-Time PCR, ELISA, immunocytochemistry, annexin V/PI, and scratching assay. Exosome treatment significantly reduce the expression level of markers related to inflammation, proliferation, migration, and angiogenesis in E-MenSCs which are aberrantly expressed in endometriosis. Moreover, apoptosis was induced in E-MenSCs after treatment which was evaluated in both gene and protein levels. In this study, we give preliminary evidence for the potential of MenSCs-Exo in ameliorating endometriosis. Regarding our results, we suggest that after relevant clinical trial, MenSCs-derived exosomes can be considered as a better treatment option to improve endometriosis compared to common and conventional treatments and show their potential as a cell-free product in endometriosis repair.
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Affiliation(s)
- Faezeh Davoodi Asl
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
| | - Seyedeh Saeideh Sahraei
- Department of Reproductive Biology, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
| | - Naser Kalhor
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
| | - Hoda Fazaeli
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
| | - Mohsen Sheykhhasan
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
| | - Sanaz Soleimani Moud
- Midwifery ward, Infertility treatment center, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
| | - Leila Naserpour
- Department of Reproductive Biology, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
| | - Azar Sheikholeslami
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran.
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14
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Torrecillas-Baena B, Pulido-Escribano V, Dorado G, Gálvez-Moreno MÁ, Camacho-Cardenosa M, Casado-Díaz A. Clinical Potential of Mesenchymal Stem Cell-Derived Exosomes in Bone Regeneration. J Clin Med 2023; 12:4385. [PMID: 37445420 DOI: 10.3390/jcm12134385] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/19/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Bone metabolism is regulated by osteoblasts, osteoclasts, osteocytes, and stem cells. Pathologies such as osteoporosis, osteoarthritis, osteonecrosis, and traumatic fractures require effective treatments that favor bone formation and regeneration. Among these, cell therapy based on mesenchymal stem cells (MSC) has been proposed. MSC are osteoprogenitors, but their regenerative activity depends in part on their paracrine properties. These are mainly mediated by extracellular vesicle (EV) secretion. EV modulates regenerative processes such as inflammation, angiogenesis, cell proliferation, migration, and differentiation. Thus, MSC-EV are currently an important tool for the development of cell-free therapies in regenerative medicine. This review describes the current knowledge of the effects of MSC-EV in the different phases of bone regeneration. MSC-EV has been used by intravenous injection, directly or in combination with different types of biomaterials, in preclinical models of bone diseases. They have shown great clinical potential in regenerative medicine applied to bone. These findings should be confirmed through standardization of protocols, a better understanding of the mechanisms of action, and appropriate clinical trials. All that will allow the translation of such cell-free therapy to human clinic applications.
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Affiliation(s)
- Bárbara Torrecillas-Baena
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
| | - Victoria Pulido-Escribano
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
| | - Gabriel Dorado
- Department Bioquímica y Biología Molecular, Campus Rabanales C6-1-E17, Campus de Excelencia Internacional Agroalimentario (ceiA3), Universidad de Córdoba, 14071 Córdoba, Spain
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), 14004 Córdoba, Spain
| | - María Ángeles Gálvez-Moreno
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
| | - Marta Camacho-Cardenosa
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
| | - Antonio Casado-Díaz
- Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), 14004 Córdoba, Spain
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15
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Sahin N, Yesil H. Regenerative methods in osteoarthritis. Best Pract Res Clin Rheumatol 2023; 37:101824. [PMID: 37244803 DOI: 10.1016/j.berh.2023.101824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 04/21/2023] [Indexed: 05/29/2023]
Abstract
Osteoarthritis (OA) is the most common type of arthritis that can affect all joint structures. The primary goals of osteoarthritis treatment are to alleviate pain, reduce functional limitations, and improve quality of life. Despite its high prevalence, treatment options for osteoarthritis are limited, with most therapeutic approaches focusing on symptom management. Tissue engineering and regenerative strategies based on biomaterials, cells, and other bioactive molecules have emerged as viable options for osteoarthritis cartilage repair. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are the most commonly used regenerative therapies today to protect, restore, or increase the function of damaged tissues. Despite promising results, there is conflicting evidence regarding the efficacy of regenerative therapies, and their efficacy remains unknown. The data suggest that more research and standardization are required for the use of these therapies in osteoarthritis. This article provides an overview of the application of MSCs and PRP applications.
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Affiliation(s)
- Nilay Sahin
- Balikesir University, Faculty of Medicine, Physical Medicine and Rehabilitation Department, Balıkesir, Turkey.
| | - Hilal Yesil
- Afyonkarahisar Health Sciences University, Faculty of Medicine, Physical Medicine and Rehabilitation Department, Afyon, Turkey.
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16
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Huo KL, Yang TY, Zhang WW, Shao J. Mesenchymal stem/stromal cells-derived exosomes for osteoporosis treatment. World J Stem Cells 2023; 15:83-89. [PMID: 37007454 PMCID: PMC10052342 DOI: 10.4252/wjsc.v15.i3.83] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/17/2023] [Accepted: 03/17/2023] [Indexed: 03/23/2023] Open
Abstract
Osteoporosis is a systemic bone disease, which leads to decreased bone mass and an increased risk of fragility fractures. Currently, there are many anti-resorption drugs and osteosynthesis drugs, which are effective in the treatment of osteoporosis, but their usage is limited due to their contraindications and side effects. In regenerative medicine, the unique repair ability of mesenchymal stem cells (MSCs) has been favored by researchers. The exosomes secreted by MSCs have signal transduction and molecular delivery mechanisms, which may have therapeutic effects. In this review, we describe the regulatory effects of MSCs-derived exosomes on osteoclasts, osteoblasts, and bone immunity. We aim to summarize the preclinical studies of exosome therapy in osteoporosis. Furthermore, we speculate that exosome therapy can be a future direction to improve bone health.
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Affiliation(s)
- Kai-Lun Huo
- Postgraduate Training Base in Shanghai Gongli Hospital, Ningxia Medical University, Yinchuan 750004, the Ningxia Hui Autonomous Region, China
| | - Tie-Yi Yang
- Department of Orthopedics, Pudong New Area Gongli Hospital, School of Medical Technology, University of Shanghai for Science and Technology, Shanghai 200135, China
| | - Wei-Wei Zhang
- Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jin Shao
- Department of Orthopedics, Pudong New Area Gongli Hospital, School of Medical Technology, University of Shanghai for Science and Technology, Shanghai 200135, China
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17
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Gerami MH, Khorram R, Rasoolzadegan S, Mardpour S, Nakhaei P, Hashemi S, Al-Naqeeb BZT, Aminian A, Samimi S. Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier. Eur J Med Res 2023; 28:86. [PMID: 36803566 PMCID: PMC9939872 DOI: 10.1186/s40001-023-01034-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 01/26/2023] [Indexed: 02/22/2023] Open
Abstract
Exosomes are membranous vesicles with a 30 to 150 nm diameter secreted by mesenchymal stem/stromal cells (MSCs) and other cells, such as immune cells and cancer cells. Exosomes convey proteins, bioactive lipids, and genetic components to recipient cells, such as microRNAs (miRNAs). Consequently, they have been implicated in regulating intercellular communication mediators under physiological and pathological circumstances. Exosomes therapy as a cell-free approach bypasses many concerns regarding the therapeutic application of stem/stromal cells, including undesirable proliferation, heterogeneity, and immunogenic effects. Indeed, exosomes have become a promising strategy to treat human diseases, particularly bone- and joint-associated musculoskeletal disorders, because of their characteristics, such as potentiated stability in circulation, biocompatibility, low immunogenicity, and toxicity. In this light, a diversity of studies have indicated that inhibiting inflammation, inducing angiogenesis, provoking osteoblast and chondrocyte proliferation and migration, and negative regulation of matrix-degrading enzymes result in bone and cartilage recovery upon administration of MSCs-derived exosomes. Notwithstanding, insufficient quantity of isolated exosomes, lack of reliable potency test, and exosomes heterogeneity hurdle their application in clinics. Herein, we will deliver an outline respecting the advantages of MSCs-derived exosomes-based therapy in common bone- and joint-associated musculoskeletal disorders. Moreover, we will have a glimpse the underlying mechanism behind the MSCs-elicited therapeutic merits in these conditions.
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Affiliation(s)
- Mohammad Hadi Gerami
- grid.412571.40000 0000 8819 4698Bone and Joint Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Roya Khorram
- grid.412571.40000 0000 8819 4698Bone and Joint Diseases Research Center, Department of Orthopedic Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Soheil Rasoolzadegan
- grid.411600.2Department of Surgery, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeid Mardpour
- grid.411705.60000 0001 0166 0922Department of Radiology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Pooria Nakhaei
- grid.411705.60000 0001 0166 0922Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Soheyla Hashemi
- grid.411036.10000 0001 1498 685XObstetrician, Gynaecology & Infertility Department, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Amir Aminian
- Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran.
| | - Sahar Samimi
- Tehran University of Medical Sciences, Tehran, Iran.
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18
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Liu X, Wei Q, Lu L, Cui S, Ma K, Zhang W, Ma F, Li H, Fu X, Zhang C. Immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles: Targeting immune cells. Front Immunol 2023; 14:1094685. [PMID: 36860847 PMCID: PMC9968735 DOI: 10.3389/fimmu.2023.1094685] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 02/01/2023] [Indexed: 02/16/2023] Open
Abstract
Various intractable inflammatory diseases caused by disorders of immune systems have pressed heavily on public health. Innate and adaptive immune cells as well as secreted cytokines and chemokines are commanders to mediate our immune systems. Therefore, restoring normal immunomodulatory responses of immune cells is crucial for the treatment of inflammatory diseases. Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are nano-sized double-membraned vesicles acting as paracrine effectors of MSCs. MSC-EVs, containing a variety of therapeutic agents, have shown great potential in immune modulation. Herein, we discuss the novel regulatory functions of MSC-EVs from different sources in the activities of innate and adaptive immune cells like macrophages, granulocytes, mast cells, natural killer (NK) cells, dendritic cells (DCs) and lymphocytes. Then, we summarize the latest clinical trials of MSC-EVs in inflammatory diseases. Furthermore, we prospect the research trend of MSC-EVs in the field of immune modulation. Despite the fact that the research on the role of MSC-EVs in regulating immune cells is in infancy, this cell-free therapy based on MSC-EVs still offers a promising solution for the treatment of inflammatory diseases.
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Affiliation(s)
- Xi Liu
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Qian Wei
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Lu Lu
- Institute of NBC Defence, PLA Army, Beijing, China
| | - Shengnan Cui
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital, Beijing, China
- Department of Dermatology, China Academy of Chinese Medical Science, Xiyuan Hospital, Beijing, China
| | - Kui Ma
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital, Beijing, China
- Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, Beijing, China
| | - Wenhua Zhang
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Fang Ma
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Haihong Li
- Department of Wound Repair, Institute of Wound Repair and Regeneration Medicine, Southern University of Science and Technology Hospital, Southern University of Science and Technology School of Medicine, Shenzhen, China
| | - Xiaobing Fu
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital, Beijing, China
- Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, Beijing, China
| | - Cuiping Zhang
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and the 4th Medical Center of Chinese PLA General Hospital, Beijing, China
- Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, Beijing, China
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19
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Xu XL, Xue Y, Ding JY, Zhu ZH, Wu XC, Song YJ, Cao YL, Tang LG, Ding DF, Xu JG. Nanodevices for deep cartilage penetration. Acta Biomater 2022; 154:23-48. [PMID: 36243371 DOI: 10.1016/j.actbio.2022.10.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 09/30/2022] [Accepted: 10/04/2022] [Indexed: 12/14/2022]
Abstract
Osteoarthritis (OA) is a degenerative joint disease and is the main cause of chronic pain and functional disability in adults. Articular cartilage is a hydrated soft tissue that is composed of normally quiescent chondrocytes at a low density, a dense network of collagen fibrils with a pore size of 60-200 nm, and aggrecan proteoglycans with high-density negative charge. Although certain drugs, nucleic acids, and proteins have the potential to slow the progression of OA and restore the joints, these treatments have not been clinically applied owing to the lack of an effective delivery system capable of breaking through the cartilage barrier. Recently, the development of nanotechnology for delivery systems renders new ideas and treatment methods viable in overcoming the limited penetration. In this review, we focus on current research on such applications of nanotechnology, including exosomes, protein-based cationic nanocarriers, cationic liposomes/solid lipid nanoparticles, amino acid-based nanocarriers, polyamide derivatives-based nanocarriers, manganese dioxide, and carbon nanotubes. Exosomes are the smallest known nanoscale extracellular vesicles, and they can quickly deliver nucleic acids or proteins to the required depth. Through electrostatic interactions, nanocarriers with appropriate balance in cationic property and particle size have a strong ability to penetrate cartilage. Although substantial preclinical evidence has been obtained, further optimization is necessary for clinical transformation. STATEMENT OF SIGNIFICANCE: The dense cartilage matrix with high-negative charge was associated with reduced therapeutic effect in osteoarthritis patients with deep pathological changes. However, a systematic review in nanodevices for deep cartilage penetration is still lacking. Current approaches to assure penetration of nanosystems into the depth of cartilage were reviewed, including nanoscale extracellular vesicles from different cell lines and nanocarriers with appropriate balance in cationic property and size particle. Moreover, nanodevices entering clinical trials and further optimization were also discussed, providing important guiding significance to future research.
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Affiliation(s)
- Xiao-Ling Xu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China
| | - Yan Xue
- Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Centre), School of Medicine, Tongji University, Shanghai 201613, China
| | - Jia-Ying Ding
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zhi-Heng Zhu
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xi-Chen Wu
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yong-Jia Song
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yue-Long Cao
- Shi's Center of Orthopedics and Traumatology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Long-Guang Tang
- International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China.
| | - Dao-Fang Ding
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Jian-Guang Xu
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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20
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MSC-EV therapy for bone/cartilage diseases. Bone Rep 2022; 17:101636. [DOI: 10.1016/j.bonr.2022.101636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 11/03/2022] [Accepted: 11/08/2022] [Indexed: 11/11/2022] Open
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21
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Luo Z, Sun Y, Qi B, Lin J, Chen Y, Xu Y, Chen J. Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis. Bioact Mater 2022; 17:344-359. [PMID: 35386460 PMCID: PMC8965035 DOI: 10.1016/j.bioactmat.2022.01.016] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 12/30/2021] [Accepted: 01/09/2022] [Indexed: 02/07/2023] Open
Abstract
Shoulder stiffness (SS) is a common shoulder disease characterized by increasing pain and limited range of motion. SS is considered to be an inflammatory and fibrotic disorder pathologically. However, there is no consensus on the most effective conservative treatment for fibrosis. Given that human Bone Marrow Mesenchymal Stem Cell-derived extracellular vesicles (BMSC-EVs) displayed promising therapeutic effects for various tissues, we investigated the therapeutic effect of BMSC-EVs on fibrosis in a mice immobilization model and two cell models. By conducting a series of experiments, we found that BMSC-EVs can significantly inhibit the fibrogenic process both in vitro and in vivo. In detail, BMSC-EVs suppressed the aberrant proliferation, high collagen production capacity, and activation of fibrotic pathways in TGF-β-stimulated fibroblasts in vitro. Besides, in vivo, BMSC-EVs reduced cell infiltration, reduced fibrotic tissue in the shoulder capsule, and improved shoulder mobility. In addition, via exosomal small RNA sequencing and qPCR analysis, let-7a-5p was verified to be the highest expressed miRNA with predicted antifibrotic capability in BMSC-EVs. The antifibrotic capacity of BMSC-EVs was significantly impaired after the knockdown of let-7a-5p. Moreover, we discovered that the mRNA of TGFBR1 (the membrane receptor of transforming growth factor β) was the target of let-7a-5p. Together, these findings elucidated the antifibrotic role of BMSC-EVs in shoulder capsular fibrosis. This study clarifies a new approach using stem cell-derived EVs therapy as an alternative to cell therapy, which may clinically benefit patients with SS in the future.
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Affiliation(s)
- Zhiwen Luo
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yaying Sun
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Beijie Qi
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Jinrong Lin
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yisheng Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yuzhen Xu
- Department of Rehabilitation, The Second Affiliated Hospital of Shandong First Medical University, Shandong Province, China
| | - Jiwu Chen
- Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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22
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Joint Tissue Protective and Immune-Modulating miRNA Landscape of Mesenchymal Stromal Cell-Derived Extracellular Vesicles under Different Osteoarthritis-Mimicking Conditions. Pharmaceutics 2022; 14:pharmaceutics14071400. [PMID: 35890296 PMCID: PMC9321932 DOI: 10.3390/pharmaceutics14071400] [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: 05/05/2022] [Revised: 06/27/2022] [Accepted: 06/29/2022] [Indexed: 01/27/2023] Open
Abstract
In regenerative medicine related to orthopedic conditions, mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) have been proposed as innovative clinical options. The definition of EV-shuttled signals and their modulation under orthopedic settings, such as osteoarthritis (OA), is crucial for MSC-related research, both for basic science and for use in clinical settings, either as therapeutics or as producers of cell-free products such as EVs or secretome. The objective of this work is to compare the literature available on high-throughput EV-miRNA data obtained from adipose-derived MSCs (ASCs) in standard conditions or cultured in high levels of IFNγ, low-level inflammatory conditions mimicking OA synovial fluid (SF), and OA-SF. The first result was that both IFNγ and low-level inflammatory treatment led to an increase, whereas SF led to a reduction in EV release. Second, more than 200 EV-miRNAs were found to be shared across the different conditions. After a bioinformatics search through experimentally validated and OA-related targets, pathways and tissues, several miRNAs resulted in the restoration of cartilage and synovium stability and the homeostasis of inflammatory cells, including macrophages, promoting their switch towards an M2 anti-inflammatory phenotype. Third, IFNγ and especially SF culturing were able to modulate the overall EV-miRNA fingerprint, although the main molecular messages related to OA resulted conserved between treatments with the majority of modulations within 2-fold range. In conclusion, ASC EV-miRNAs may be modulated in their overall landscape by OA-related culturing conditions albeit resulted largely stable in their specific OA-protective signals allowing for a faster clinical translation of these new cell-free therapies for joint diseases.
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23
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Lee SY, Lee JW. 3D Spheroid Cultures of Stem Cells and Exosome Applications for Cartilage Repair. LIFE (BASEL, SWITZERLAND) 2022; 12:life12070939. [PMID: 35888029 PMCID: PMC9317836 DOI: 10.3390/life12070939] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/20/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022]
Abstract
Cartilage is a connective tissue that constitutes the structure of the body and consists of chondrocytes that produce considerable collagenous extracellular matrix and plentiful ground substances, such as proteoglycan and elastin fibers. Self-repair is difficult when the cartilage is damaged because of insufficient blood supply, low cellularity, and limited progenitor cell numbers. Therefore, three-dimensional (3D) culture systems, including pellet culture, hanging droplets, liquid overlays, self-injury, and spinner culture, have attracted attention. In particular, 3D spheroid culture strategies can enhance the yield of exosome production of mesenchymal stem cells (MSCs) when compared to two-dimensional culture, and can improve cellular restorative function by enhancing the paracrine effects of MSCs. Exosomes are membrane-bound extracellular vesicles, which are intercellular communication systems that carry RNAs and proteins. Information transfer affects the phenotype of recipient cells. MSC-derived exosomes can facilitate cartilage repair by promoting chondrogenic differentiation and proliferation. In this article, we reviewed recent major advances in the application of 3D culture techniques, cartilage regeneration with stem cells using 3D spheroid culture system, the effect of exosomes on chondrogenic differentiation, and chondrogenic-specific markers related to stem cell derived exosomes. Furthermore, the utilization of MSC-derived exosomes to enhance chondrogenic differentiation for osteoarthritis is discussed. If more mechanistic studies at the molecular level are conducted, MSC-spheroid-derived exosomes will supply a better therapeutic option to improve osteoarthritis.
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Affiliation(s)
- Seung Yeon Lee
- Department of Molecular Medicine, College of Medicine, Gachon University, 155, Gaetbeol-ro, Yeonsu-ku, Incheon 21999, Korea;
| | - Jin Woo Lee
- Department of Molecular Medicine, College of Medicine, Gachon University, 155, Gaetbeol-ro, Yeonsu-ku, Incheon 21999, Korea;
- Department of Health Sciences and Technology, GAIHST, Gachon University, 155, Gaetbeol-ro, Yeonsu-ku, Incheon 21999, Korea
- Correspondence: ; Tel.: +82-32-899-6516; Fax: +82-32-899-6039
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24
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Yan B, Lv S, Tong P, Yan L, Chen Z, Zhou L, Yuan Q, Guo L, Shan L. Intra-Articular Injection of Adipose-Derived Stem Cells Ameliorates Pain and Cartilage Anabolism/Catabolism in Osteoarthritis: Preclinical and Clinical Evidences. Front Pharmacol 2022; 13:854025. [PMID: 35387326 PMCID: PMC8978713 DOI: 10.3389/fphar.2022.854025] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/28/2022] [Indexed: 12/27/2022] Open
Abstract
Background: Osteoarthritis (OA) is the most common joint disorder, lacking disease-modifying treatments. Adipose-derived mesenchymal stem cells (ADSCs) are adult multipotent stromal cells obtained from fat tissue, which holds great potential in treating OA. This study aimed to evaluate the anti-OA efficacy of ADSCs from preclinical and clinical facets and explore the underlying mechanism of action. Methods:In vivo, a single dose of 5 × 105 ADSCs was injected into the knee joints of monoiodoacetate-induced OA rat model. The levels of metabolic and hypertrophic molecules (MMP13, Collagen II, Collagen X) of chondrocytes were measured by immunohistochemistry. In vitro, cell viability assay was conducted to detect the proliferation ability of chondrocytes treated with ADSCs conditioned medium (ADSCs-CM). Quantitative real-time polymerase chain reaction and Western blot assays were applied to explore the mechanism of action of ADSCs. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of ADSCs on OA patients. Results: The animal study showed that ADSCs significantly alleviated OA cartilage lesions in rats, as was confirmed by downregulation of the MMP13 and Collagen X and upregulation of the Collagen II. In vitro data showed that ADSCs-CM promoted the proliferation of chondrocytes, and significantly restored the IL-1β-induced abnormal expressions of molecular markers IL-6, Aggrecan, MMP3, MMP13, Collagen II, Collagen X, ADAMTS5, ADAMTS9, SOX6, and SOX9 in chondrocytes. Such regulatory effects of ADSCs-CM on the proliferation and these anabolic, catabolic, and hypertrophic markers of chondrocytes suggested a paracrine-based mode of action of ADSCs. Furthermore, the clinical data showed that ADSCs reduced pain and repaired cartilage damage in OA patients, with no adverse events. Conclusion: This study demonstrated the anti-OA efficacy, safety, and a paracrine-based mechanism of ADSCs, providing a promising cell-based therapeutic option for OA treatment.
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Affiliation(s)
- Bo Yan
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.,The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.,Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, China
| | - Shuaijie Lv
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
| | - Peijian Tong
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
| | - Li Yan
- Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, China
| | - Zuxiang Chen
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
| | - Li Zhou
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiang Yuan
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Le Guo
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.,Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, China
| | - Letian Shan
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.,Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, China
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