General research on joints Scientific Publications

Latest publication 08/26/2022

Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tend

Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance. The therapeutic effect of stem cell...

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    [title] => Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tend
    [paragraph] => Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathy via regulating macrophage heterogeneity
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Authors
T Ye, Z Chen, J Zhang et al

 Lab
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Journal
Bioactive Materials
Abstract
Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance. The therapeutic effect of stem cell derived-small extracellular vesicles (sEVs) for tendinopathy has been validated in recent years. However, whether large extracellular vesicles (lEVs), another subset of extracellular vesicles, possesses the ability for the improvement of tendinopathy remains unknown. Here, we showed that lEVs secreted from iPSC-derived MSCs (iMSC-lEVs) significantly mitigated pain derived from tendinopathy in rats. Immunohistochemical analysis showed that iMSC-lEVs regulated the heterogeneity of infiltrated macrophages and several inflammatory cytokines in rat tendon tissue. Meanwhile, in vitro experiments revealed that the M1 pro-inflammatory macrophages were repolarized towards M2 anti-inflammatory macrophages by iMSC-lEVs, and this effect was mediated by regulating p38 MAPK pathway. Moreover, liquid chromatography-tandem mass spectrometry analysis identified 2208 proteins encapsulated in iMSC-lEVs, including 134 new-found proteins beyond current Vesiclepedia database. By bioinformatics and Western blot analyses, we showed that DUSP2 and DUSP3, the negative regulator of p38 phosphorylation, were enriched in iMSC-lEVs and could be transported to macrophages. Further, the immunomodulatory effect of iMSC-lEVs on macrophages was validated in explant tendon tissue from tendinopathy patients. Taken together, our results demonstrate that iMSC-lEVs could reduce inflammation in tendinopathy by regulating macrophage heterogeneity, which is mediated via the p38 MAPK pathway by delivery of DUSP2 and DUSP3, and might be a promising candidate for tendinopathy therapy.
BIOSEB Instruments Used
Static Weight Bearing Touch: Incapacitance Test (BIO-SWB-TOUCH-M)
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An easy and non pain-inducing solution for assessing the level of discomfort (incapacitance) in the injured paw of a small animal like a rat or a mouse by measuring the Postural Equilibrium “ independently of the operator". The static weight bearing instrument is ideal for your research on analagesia and nociception involving rodents: osteo arthrisis, cartilage degeneration, inflammation models, nerve injury models, and much more... Discover the SWB-Touch: now with a brand new touch-screen console!

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