Journal ArticleDOI
Exosomal KLF3-AS1 from hMSCs promoted cartilage repair and chondrocyte proliferation in osteoarthritis.
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TLDR
In vivo investigation indicated that exosomal KLF3-AS1 promoted cartilage repair and chondrocyte proliferation in a rat model of OA, which might be an underlying therapeutic target for OA.Abstract:
The present study was designed to explore whether exosomal lncRNA-KLF3-AS1 derived from human mesenchymal stem cells (hMSCs) can serve as a positive treatment for osteoarthritis (OA). hMSCs and MSC-derived exosomes (MSC-exo) were prepared for morphological observation and identification by transmission electron microscopy and flow cytometry. IL-1β-induced OA chondrocytes and collagenase-induced rat model of OA were established for the further experiments. Lentivirus-mediated siRNA targeting KLF3-AS1 was transfected into MSCs for silencing KLF3-AS1. The real-time quantitative PCR and western blotting analysis were performed to examine the mRNA and protein levels of type II collagen alpha 1 (Col2a1), aggrecan, matrix metalloproteinase 13 and runt-related transcription factor 2. Cell proliferation, apoptosis and migration were evaluated by CCK-8 assay, flow cytometry and transwell assay. HE (hematoxylin and eosin) staining and immunohistochemistry were used for histopathological studies. MSC-exo ameliorated IL-1β-induced cartilage injury. Furthermore, lncRNA KLF3-AS1 was markedly enriched in MSC-exo, and exosomal KLF3-AS1 suppressed IL-1β-induced apoptosis of chondrocytes. Further in vivo investigation indicated that exosomal KLF3-AS1 promoted cartilage repair in a rat model of OA. Exosomal KLF3-AS1 promoted cartilage repair and chondrocyte proliferation in a rat model of OA, which might be an underlying therapeutic target for OA.read more
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Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome
Carl Randall Harrell,Crissy Fellabaum,Nemanja Jovicic,Valentin Djonov,Nebojsa Arsenijevic,Vladislav Volarevic +5 more
TL;DR: Therapeutic effects of MSC-sourced secretomes relied on their capacity to deliver genetic material, growth and immunomodulatory factors to the target cells enabling activation of anti-apoptotic and pro-survival pathways that resulted in tissue repair and regeneration.
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Mesenchymal stem cell-based therapy of osteoarthritis: Current knowledge and future perspectives.
C. Randall Harrell,Bojana Simovic Markovic,Crissy Fellabaum,Aleksandar Arsenijevic,Vladislav Volarevic +4 more
TL;DR: Current knowledge and future perspectives regarding molecular and cellular mechanisms responsible for beneficial effects of autologous and allogeneic MSCs in the treatment of OA are emphasized.
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Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role of the Cell Secretome.
TL;DR: An overview of the functions and mechanisms of MSC-secreted molecules found to be upregulated in models of OA, whether using in vitro or in vivo models is provided.
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LncRNA KLF3-AS1 in human mesenchymal stem cell-derived exosomes ameliorates pyroptosis of cardiomyocytes and myocardial infarction through miR-138-5p/Sirt1 axis
TL;DR: LncRNA KLF3-AS1 in exosomes secreted from hMSCs by acting as a ceRNA to sponge miR-138-5p can regulate Sirt1 so as to inhibit cell pyroptosis and attenuate MI progression.
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Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis
Lei He,Tianwei He,Jianghao Xing,Qing Zhou,Lei Fan,Can Liu,Yuyong Chen,Depeng Wu,Zhenming Tian,Bin Liu,Limin Rong +10 more
TL;DR: BMSC-derived exosomes can effectively promote cartilage repair and extracellular matrix synthesis, as well as alleviate knee pain in the OA rats.
References
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Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
TL;DR: It is shown that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location, and it is proposed that this RNA is called “exosomal shuttle RNA” (esRNA).
Journal ArticleDOI
Clinical Trials with Mesenchymal Stem Cells: An Update:
TL;DR: Clinical trials using MSCs for representative diseases, including hematological disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney, and lung are analyzed, as well as cardiovascular, bone and cartilage, neurological, and autoimmune diseases.
Journal ArticleDOI
Mesenchymal Stem Cell Exosomes Induce Proliferation and Migration of Normal and Chronic Wound Fibroblasts, and Enhance Angiogenesis In Vitro
TL;DR: It is found that MSC exosomes ranged from 30 to 100-nm in diameter and internalization of MSCExosomes resulted in a dose-dependent enhancement of proliferation and migration of fibroblasts derived from normal donors and chronic wound patients.
Journal ArticleDOI
Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration
Shipin Zhang,Wern Cui Chu,Ruenn Chai Lai,Sai Kiang Lim,Sai Kiang Lim,James Hoi Po Hui,Wei Seong Toh +6 more
TL;DR: This study demonstrates for the first time the efficacy of human embryonic MSCExosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and 'cell-free' therapeutic alternative to cell-based MSC therapy.
Journal ArticleDOI
Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model.
TL;DR: SMSC-140-Exos enhanced the proliferation and migration of ACs without damaging ECM secretion in vitro, while in vivo, SMSC- 140- exos successfully prevented OA in a rat model.