한빛사 논문
Chang Hee Wooa,b, Hark Kyun Kimc , Gun Young Jungc , Youn Jae Junga,b, Kyoung Soo Leea , Ye Eun Yuna , Jihoon Hanc , Jeongmi Leec , Woo Sung Kima , Ji Suk Choib , Siyoung Yangd , Jae Hyung Parkb,e,f,g, Dong-Gyu Job,c,f,g,*, and Yong Woo Choa,b,*
aDepartment of Chemical Engineering, Hanyang University, Ansan, Korea; bResearch Institute, Exostemtech Inc, Ansan, Korea; cSchool of Pharmacy, Sungkyunkwan University, Suwon, Korea; dDepartment of pharmacology, Ajou University School of Medicine, Suwon, Korea; eSchool of Chemical Engineering, Sungkyunkwan University, Suwon, Korea; fSamsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Suwon, Korea; gBiomedical Institute for Convergence, Sungkyunkwan University, Suwon, Korea
*Corresponding author.
Abstract
Osteoarthritis (OA) is a chronic degenerative disease of articular cartilage that is the most common joint disease worldwide. Mesenchymal stem cells (MSCs) have been the most extensively explored for the treatment of OA. Recently, it has been demonstrated that MSC-derived extracellular vesicles (EVs) may contribute to the potential mechanisms of MSC-based therapies. In this study, we investigated the therapeutic potential of human adipose-derived stem cells EVs (hASC-EVs) in alleviating OA, along with the mechanism. EVs were isolated from the culture supernatants of hASCs by a multi-filtration system based on the tangential flow filtration (TFF) system. The isolated EVs were characterised using dynamic light scattering (DLS), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and flow cytometry analysis. The hASC-EVs not only promoted the proliferation and migration of human OA chondrocytes, but also maintained the chondrocyte matrix by increasing type Ⅱ collagen synthesis and decreasing MMP-1, MMP-3, MMP-13 and ADAMTS-5 expression in the presence of IL-1β in vitro. Intra-articular injection of hASC-EVs significantly attenuated OA progression and protected cartilage from degeneration in both the monosodium iodoacetate (MIA) rat and the surgical destabilisation of the medial meniscus (DMM) mouse models. In addition, administration of hASC-EVs inhibited the infiltration of M1 macrophages into the synovium. Overall results suggest that the hASC-EVs should be considered as a potential therapeutic approach in the treatment of OA.
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