Synovial fluid-derived mesenchymal cells have non-inferior chondrogenic potential and can be utilized for regenerative therapy as substitute for synovium-derived cells

Amemiya, Miki; Tsuji, Kunikazu; Katagiri, Hiroki; Miyatake, Kazumasa; Nakagawa, Yusuke; Sekiya, Ichiro; Muneta, Takeshi; Koga, Hideyuki

doi:10.1016/j.bbrc.2019.12.068

Cited by 20 publications

(17 citation statements)

References 27 publications

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“…Larger studies investigating more SF analytes and SF MSC transcripts using the same cohort of patients (validation cohort), ideally at more time-points, during the course of distraction and comparing responders and non-responders, would be needed to shed more light on the effects of joint off-loading on SF cellular and molecular responses. Changes in SF MSC secretome and their immunomodulation, chondrogenic and chondroprotective potencies using appropriate assays (Cassano et al, 2018;Amemiya et al, 2020;Watanabe et al, 2020) would be needed to confirm the functional significance of the observed transcript changes. In addition to MSCs, the investigations of SF immune cells, and particularly macrophage subsets in terms of their pro-and anti-inflammatory polarization states (Fahy et al, 2014;Daghestani et al, 2015), would be necessary.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction

Sanjurjo‐Rodríguez

Altaie

Mastbergen

et al. 2020

Front. Bioeng. Biotechnol.

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Synovial Fluid MSC Gene Expression (weeks 3 and 6). Additionally, early KJD changes (week 3) were marked by significant increases in MSC chondrogenic commitment markers gremlin 1 (GREM1) and growth differentiation factor 5 (GDF5). In combination, our results reveal distinct transcriptomes on joint-resident MSCs from different biomechanical environments and show that 6week joint off-loading leads to transcriptional changes in SF MSCs that may be beneficial for cartilage regeneration. Biomechanical factors should be certainly considered in the development of novel MSC-based therapies for OA.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction

Sanjurjo‐Rodríguez

Altaie

Mastbergen

et al. 2020

Front. Bioeng. Biotechnol.

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“…The pellet wet weight is an important index to evaluate the chondrogenesis potential of a population of MSCs in vitro. Some researchers quantitatively compared the differentiation potential of MSCs from bone marrow, synovium, periosteum, adipose tissue, and muscle, which showed that SM-MSCs have the greatest differentiation potential among the mesenchymal tissue-derived cells examined [ 34 , 43 ]. Compared with subcutaneous fat-derived MSCs, SM-MSCs have the same lipogenic ability but higher chondrogenic and osteogenic ability, colony-forming efficiency, and expansion ability [ 8 ].…”

Section: Biological Characteristics Of Sm-mscsmentioning

confidence: 99%

Synovial membrane mesenchymal stem cells: past life, current situation, and application in bone and joint diseases

Gao

et al. 2020

Stem Cell Res Ther

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Mesenchymal stem cells (MSCs) can be isolated from not only bone marrow, but also various adult mesenchymal tissues such as periosteum, skeletal muscle, and adipose tissue. MSCs from different tissue sources have different molecular phenotypes and differentiation potential. Synovial membrane (SM) is an important and highly specific component of synovial joints. Previous studies have suggested that the synovium is a structure with a few cell layers thick and consists mainly of fibroblast-like synoviocytes (FLS), which forms a layer that lining the synovial membrane on the joint cavity and synovial fluid through cell-cell contact. In recent years, studies have found that there are also mesenchymal stem cells in the synovium, and as an important part of the mesenchymal stem cell family, it has strong capabilities of cartilage forming and tissue repairing. This article reviews the sources, surface markers, subtypes, influencing factors, and applications in inflammatory joints of synovial membrane mesenchymal stem cells (SM-MSCs) in recent years, aiming to clarify the research status and existing problems of SM-MSCs.

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“…All human procedures were approved by the Local Ethical Committee for Human Research (Tokyo Medical and Dental University, Tokyo, Japan; Approval No.2121). Synovial MSCs were isolated and cultured from the synovium, as previously described [ 26 ]. Briefly, the synovia were harvested from patients who provided written, informed consent to participate in this research prior to undergoing anterior cruciate ligament reconstruction.…”

Section: Methodsmentioning

confidence: 99%

Extracellular vesicles derived from mesenchymal stromal cells mediate endogenous cell growth and migration via the CXCL5 and CXCL6/CXCR2 axes and repair menisci

et al. 2021

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Background Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are promising candidates for tissue regeneration therapy. However, the therapeutic efficacy of MSC-EVs for meniscus regeneration is uncertain, and the mechanisms underlying MSC-EV-mediated tissue regeneration have not been fully elucidated. The aims of this study were to evaluate the therapeutic efficacy of intra-articular MSC-EV injection in a meniscus defect model and elucidate the mechanism underlying MSC-EV-mediated tissue regeneration via combined bioinformatic analyses. Methods MSC-EVs were isolated from human synovial MSC culture supernatants via ultrafiltration. To evaluate the meniscus regeneration ability, MSC-EVs were injected intra-articularly in the mouse meniscus defect model immediately after meniscus resection and weekly thereafter. After 1 and 3 weeks, their knees were excised for histological and immunohistochemical evaluations. To investigate the mechanisms through which MSC-EVs accelerate meniscus regeneration, cell growth, migration, and chondrogenesis assays were performed using treated and untreated chondrocytes and synovial MSCs with or without MSC-EVs. RNA sequencing assessed the gene expression profile of chondrocytes stimulated by MSC-EVs. Antagonists of the human chemokine CXCR2 receptor (SB265610) were used to determine the role of CXCR2 on chondrocyte cell growth and migration induced by MSC-EVs. Results In the meniscus defect model, MSC-EV injection accelerated meniscus regeneration and normalized the morphology and composition of the repaired tissue. MSC-EVs stimulated chondrocyte and synovial MSC cell growth and migration. RNA sequencing revealed that MSC-EVs induced 168 differentially expressed genes in the chondrocytes and significantly upregulated CXCL5 and CXCL6 in chondrocytes and synovial MSCs. Suppression of CXCL5 and CXCL6 and antagonism of the CXCR2 receptor binding CXCL5 and CXCL6 negated the influence of MSC-EVs on chondrocyte cell growth and migration. Conclusions Intra-articular MSC-EV administration repaired meniscus defects and augmented chondrocyte and synovial MSC cell growth and migration. Comprehensive transcriptome/RNA sequencing data confirmed that MSC-EVs upregulated CXCL5 and CXCL6 in chondrocytes and mediated the cell growth and migration of these cells via the CXCR2 axis.

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Synovial fluid-derived mesenchymal cells have non-inferior chondrogenic potential and can be utilized for regenerative therapy as substitute for synovium-derived cells

Cited by 20 publications

References 27 publications

Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction

Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction

Synovial membrane mesenchymal stem cells: past life, current situation, and application in bone and joint diseases

Extracellular vesicles derived from mesenchymal stromal cells mediate endogenous cell growth and migration via the CXCL5 and CXCL6/CXCR2 axes and repair menisci

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