Immunomodulation of MSCs and MSC-Derived Extracellular Vesicles in Osteoarthritis

Zhao, Xige; Zhao, Yanhong; Sun, Xiaojuan; Xing, Yi; Wang, Xing; Yang, Qiang

doi:10.3389/fbioe.2020.575057

Cited by 87 publications

(74 citation statements)

References 122 publications

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“…Thus far, the vital roles of MSCs-EVs have been demonstrated in many diseases. MSCs-EVs could restrain chondrocyte apoptosis and promote chondrocyte proliferation [ 64 – 66 ]. In recent years, an increasing number of studies have provided strong evidence that MSCs-EVs could participate in the repair process by transporting functional proteins or RNA.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

Liu

et al. 2021

J Nanobiotechnol

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Background Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) may play a vital role in a variety of biological processes, including cartilage regeneration. However, few studies reported their potential in the development of osteoarthritis (OA) previously. In this study, we explored the biological roles and underlying mechanism of MSCs-EVs in OA. Results Co-culture experiments revealed that MSCs-EVs could promote the expression of collagen type II alpha 1 chain (COL2A1), SRY-box transcription factor 9 (SOX9) and Aggrecan while negatively regulate the expression of chondrocyte hypertrophy markers matrix metallopeptidase 13 (MMP-13) and RUNX family transcription factor 2 (Runx2) in mouse chondrocytes in the OA model. Besides, the results of cell experiments indicated that MSCs-EVs could notably weaken the suppression of chondrocyte proliferation, migration and the promotion of chondrocyte apoptosis via interleukin1β (IL-1β) induction. In addition, MSCs-circHIPK3-EVs (EVs derived from MSCs overexpressing circHIPK3) considerably improved IL-1β-induced chondrocyte injury. Mechanistically, we elucidated that circHIPK3 could directly bind to miR-124-3p and subsequently elevate the expression of the target gene MYH9. Conclusion The findings in our study demonstrated that EVs-circHIPK3 participated in MSCs-EVs-mediated chondrocyte proliferation and migration induction and in chondrocyte apoptosis inhibition via the miR-124-3p/MYH9 axis. This offers a promising novel cell-free therapy for treating OA. Graphic abstract

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

Liu

et al. 2021

J Nanobiotechnol

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“…MSCs are known to have significant immunomodulatory capabilities which are suspected to underpin a significant proportion of their therapeutic efficacy [45]. These properties are partially mediated by the secretion of a range of bioactive substances, including growth factors, cytokines and chemokines [45][46][47]. Of the cytokines produced and secreted by MSCs, TGF-β is one of the most prominent.…”

Section: Discussionmentioning

confidence: 99%

An In Vitro System to Study the Effect of Subchondral Bone Health on Articular Cartilage Repair in Humans

Hopkins

Wright

Kuiper

et al. 2021

Cells

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Chondrocyte-based cartilage repair strategies, such as articular chondrocyte implantation, are widely used, but few studies addressed the communication between native subchondral bone cells and the transplanted chondrocytes. An indirect co-culture model was developed, representing a chondrocyte/scaffold-construct repair of a cartilage defect adjoining bone, where the bone could have varying degrees of degeneration. Human BM-MSCs were isolated from two areas of subchondral bone in each of five osteochondral tissue specimens from five patients undergoing knee arthroplasty. These two areas underlaid the macroscopically and histologically best and worst cartilage, representing early and late-stage OA, respectively. BM-MSCs were co-cultured with normal chondrocytes suspended in agarose, with the two cell types separated by a porous membrane. After 0, 7, 14 and 21 days, chondrocyte–agarose scaffolds were assessed by gene expression and biochemical analyses, and the abundance of selected proteins in conditioned media was assessed by ELISA. Co-culture with late-OA BM-MSCs resulted in a reduction in GAG deposition and a decreased expression of genes encoding matrix-specific proteins (COL2A1 and ACAN), compared to culturing with early OA BM-MSCs. The concentration of TGF-β1 was significantly higher in the early OA conditioned media. The results of this study have clinical implications for cartilage repair, suggesting that the health of the subchondral bone may influence the outcomes of chondrocyte-based repair strategies.

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“…Although cell reconstitution is an essential component of MSC-based tissue engineering application, the therapeutic [68] and protective effect of MSCs is now mainly thought to derive from their secreted factors enhancing cell survival [69] and from intrinsic immunomodulatory functions [70]. MSCs possess immunomodulatory [71,72] and immunosuppressive [73] properties, and thanks to the low expression of the major histocompatibility complex (MHC) class I and almost absent MHC II, they are considered immune privileged cells upon isolation, a state that could be progressively lost during in vitro cell maintenance.…”

Section: Mscs As Source Of Antibiotic-free Nanomaterialsmentioning

confidence: 99%

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

Marrazzo

Pizzuti

Zia³

et al. 2021

Antibiotics

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Antibiotic resistance is creating enormous attention on the development of new antibiotic-free therapy strategies for bacterial diseases. Mesenchymal stromal stem cells (MSCs) are the most promising candidates in current clinical trials and included in several cell-therapy protocols. Together with the well-known immunomodulatory and regenerative potential of the MSC secretome, these cells have shown direct and indirect anti-bacterial effects. However, the low reproducibility and standardization of MSCs from different sources are the current limitations prior to the purification of cell-free secreted antimicrobial peptides and exosomes. In order to improve MSC characterization, novel label-free functional tests, evaluating the biophysical properties of the cells, will be advantageous for their cell profiling, population sorting, and quality control. We discuss the potential of emerging microfluidic technologies providing new insights into density, shape, and size of live cells, starting from heterogeneous or 3D cultured samples. The prospective application of these technologies to studying MSC populations may contribute to developing new biopharmaceutical strategies with a view to naturally overcoming bacterial defense mechanisms.

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Immunomodulation of MSCs and MSC-Derived Extracellular Vesicles in Osteoarthritis

Cited by 87 publications

References 122 publications

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

An In Vitro System to Study the Effect of Subchondral Bone Health on Articular Cartilage Repair in Humans

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

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