Effects of human umbilical cord mesenchymal stem cell-derived exosomes in the rat osteoarthritis models

Author:

Yang Huanfeng12,Zhou Yiqin3,Ying Bi2,Dong Xuhui2ORCID,Qian Qirong3,Gao Shaorong145ORCID

Affiliation:

1. Tongji University Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, , Shanghai, 200120, People’s Republic of China

2. Oricell Therapeutics Department of R&D, , Shanghai, 201203, People’s Republic of China

3. Shanghai Changzheng Hospital, Naval Medical University Department of Orthopedics, , Shanghai, 200003, People’s Republic of China

4. Tongji University Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translation Research Center, Shanghai First Maternity and Infant Hospital, School of Life Science and Technology, , Shanghai, 201204, People’s Republic of China

5. Tongji University Frontier Science Center for Stem Cell Research, , Shanghai, 200092, People’s Republic of China

Abstract

Abstract Mesenchymal stem cells (MSCs) offer great potential for treatment of osteoarthritis (OA) by promoting articular cartilage regeneration via paracrine secretion of exosomes; however, the underlying mechanisms are not fully understood. This study aimed to explore the therapeutic effects of exosomes secreted by human umbilical cord-derived MSCs (hUC-MSCs) in rat models of OA and reveal the underlying mechanisms. UC-MSCs and UC-MSC-exosomes were prepared and identified by transmission electron microscopy and flow cytometry. IL-1β-induced OA chondrocytes and the operation and collagenase-induced OA rat models were established. The results of micro-computed tomography, histology, and immunohistochemistry showed that UC-MSC-exosomes promoted cartilage regeneration in OA rats. ELISA results showed that the levels of synovial fluid cytokines, TNF-α, IL-1β, and IL-6, were lower in exosome therapy group than control group in both OA rat models. Exosome treatment significantly downregulated the expression of MMP-13 and ADAMTS-5 in chondrocytes stimulated by IL-1β, and upregulated collagen II expression. These findings suggest that hUC-MSC-exosomes offer a promising option for the therapy for OA.

Publisher

Oxford University Press (OUP)

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