Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats

Ozeki, Nobutake; Muneta, Takeshi; Koga, Hideyuki; Nakagawa, Yusuke; Mizuno, Mitsuru; Tsuji, Kunikazu; Mabuchi, Yo; Akazawa, Chihiro; Kobayashi, Eiji; Matsumoto, Kenji; Futamura, Kenta; Saito, T.; Sekiya, Ichiro

doi:10.1016/j.joca.2015.12.018

Cited by 160 publications

(138 citation statements)

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“…SMMSCs were also reported to have a greater capacity to stimulate chondrogenesis than BMSCs and AMSCs, making them more suitable for cartilage repair [19]. Recent studies have highlighted the role of SMMSCs for the treatment of OA, and one study reported that SMMSCs inhibited OA progression in rats [16]. However, the effect of SMMSC-Exos on OA repair has not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, researchers have demonstrated that synovial membrane-derived MSCs (SMMSCs) can inhibit OA progression [15, 16]. SMMSCs are particularly well suited for cartilage repair because the synovium and cartilage originate from a common pool of cells during the development of synovial joints [17, 18], suggesting that SMMSCs are developmentally more closely related to chondrocytes than to other MSCs.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis

et al. 2017

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BackgroundOsteoarthritis (OA) is the most common joint disease worldwide. In the past decade, mesenchymal stem cells (MSCs) have been used widely for the treatment of OA. A potential mechanism of MSC-based therapies has been attributed to the paracrine secretion of trophic factors, in which exosomes may play a major role. In this study, we aimed to compare the effectiveness of exosomes secreted by synovial membrane MSCs (SMMSC-Exos) and exosomes secreted by induced pluripotent stem cell-derived MSCs (iMSC-Exos) on the treatment of OA.MethodsInduced pluripotent stem cell-derived MSCs and synovial membrane MSCs were characterized by flow cytometry. iMSC-Exos and SMMSC-Exos were isolated using an ultrafiltration method. Tunable resistive pulse-sensing analysis, transmission electron microscopy, and western blots were used to identify exosomes. iMSC-Exos and SMMSC-Exos were injected intra-articularly in a mouse model of collagenase-induced OA and the efficacy of exosome injections was assessed by macroscopic, histological, and immunohistochemistry analysis. We also evaluated the effects of iMSC-Exos and SMMSC-Exos on proliferation and migration of human chondrocytes by cell-counting and scratch assays, respectively.ResultsThe majority of iMSC-Exos and SMMSC-Exos were approximately 50–150 nm in diameter and expressed CD9, CD63, and TSG101. The injection of iMSC-Exos and SMMSC-Exos both attenuated OA in the mouse OA model, but iMSC-Exos had a superior therapeutic effect compared with SMMSC-Exos. Similarly, chondrocyte migration and proliferation were stimulated by both iMSC-Exos and SMMSC-Exos, with iMSC-Exos exerting a stronger effect.ConclusionsThe present study demonstrated that iMSC-Exos have a greater therapeutic effect on OA than SMMSC-Exos. Because autologous iMSCs are theoretically inexhaustible, iMSC-Exos may represent a novel therapeutic approach for the treatment of OA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0510-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis

et al. 2017

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“…In a rat knee OA model, S-MSCs injected weekly, rather than at a single time, were found to have migrated into the synovium and retained their undifferentiated S-MSC properties. The S-MSCs increased genetic expression of chondroprotective proteins such as BMP-2 and an antiinflammatory gene, TSG-6 [60]. This suggests that periodic injections of S-MSCs can allow the MSCs to retain their MSC properties as well as inhibit the advancement of OA through genetic transcription.…”

Section: Synovial-derived Mesenchymal Stem Cells (S-mscs)mentioning

confidence: 95%

Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis

Burke

Hunter

Kolhe

et al. 2016

Clinical & Translational Med

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Osteoarthritis (OA) is a chronic degenerative disease affecting articular cartilage in joints, and it is a leading cause of disability in the United States. Current pharmacological treatment strategies are ineffective to prevent the OA progression; however, cellular therapies have the potential to regenerate the lost cartilage, combat cartilage degeneration, provide pain relief, and improve patient mobility. One of the most promising sources of cellular regenerative medicine is from mesenchymal stem cells (MSCs). MSCs can be isolated from adipose tissue, bone marrow, synovial tissue, and other sources. The aim of this review is to compile recent advancement in cellular based therapy more specifically in relation to MSCs in the treatment of osteoarthritis.

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“…For many years, cartilage damage has been considered to be the main pathogenesis of OA. However, with the deepening of research, the important role of soft tissues around the joints such as synovial tissues and fat pad in the pathogenesis of OA has been recognized more and more [2,[5][6][7]. Recent studies have pointed out that synovial inflammation is a precursor to radiological OA [8], has a significant positive correlation with OA symptoms [9], and further aggravates cartilage damage [10].…”

Section: Introductionmentioning

confidence: 99%

Extraction and identification of synovial tissue-derived exosomes by different separation techniques

et al. 2020

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Objective: The aim of this study is to compare the efficiency of different separation techniques for extracting synovial tissue-derived exosomes. Methods: The synovial tissue discarded during knee arthroscopy or total knee arthroplasty surgery was collected from the Third Affiliated Hospital of Beijing University of Chinese Medicine. Ultracentrifugation (UC), filtration combined with size exclusion chromatography (SECF), and 8% polyethylene glycol (PEG) were used to extract synovial tissue-derived exosomes. Transmission electron microscopy (TEM), nanoparticle tracer analysis (NTA), and Western Blot (WB) were used to detect the morphology, particle size, and biomarker proteins (CD9, CD63, Flotillin-1, and calnexin) of exosomes. Results: The extracts of enriched round and discoid vesicles were successfully extracted with UC, SECF, and PEG. The results of TEM have shown that all three extraction methods can extract circular or elliptical vesicles with discand cup-shaped structures from the synovial tissue, with the diameter is about 30-150 nm. NTA suggested the main peaks of three groups of exosomes are around 100-120 nm, and the concentration of the three groups of exosomes was greater than 1 × 10 10 /ml. The results of WB showed that three positive protein markers (CD9, CD63, and Flotillin-1) were highly expressed in the suspension extracted by the three methods and low in the synovial tissue. However, the negative protein (calnexin) was highly expressed in synovial tissues and PEG group, while low in UC and SECF group. Conclusion: Morphology, particle size, and labeled protein marker detection confirmed that UC, SECF, and PEG can extract exosomes derived from synovial tissue; UC and SECF are more recommended for the extraction of synovial tissue-derived exosomes, which provides a methodological basis for studying the function and mechanism of synovial tissue exosomes in the future.

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Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats

Abstract: Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors.

Cited by 160 publications

References 46 publications

Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis

Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis

Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis

Extraction and identification of synovial tissue-derived exosomes by different separation techniques

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