AUTHOR=Nguyen Thu Huyen , Dao Huy Hoang , Duong Chau Minh , Nguyen Xuan-Hung , Hoang Diem Huong , Do Xuan-Hai , Truong Trung Quang , Nguyen Tu Dac , Nguyen Liem Thanh , Than Uyen Thi Trang 

TITLE=Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1041592

DOI=10.3389/fimmu.2022.1041592

ISSN=1664-3224

ABSTRACT=<p>In recent years, extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) have emerged as a potential cell-free therapy against osteoarthritis (OA). Thus, we investigated the therapeutic effects of EVs released by cytokine-primed umbilical cord-derived MSCs (UCMSCs) on osteoarthritic chondrocyte physiology. Priming UCMSCs individually with transforming growth factor beta (TGFβ), interferon alpha (IFNα), or tumor necrosis factor alpha (TNFα) significantly reduced the sorting of miR-181b-3p but not miR-320a-3p; two negative regulators of chondrocyte regeneration, into EVs. However, the EV treatment did not show any significant effect on chondrocyte proliferation. Meanwhile, EVs from both non-priming and cytokine-primed UCMSCs induced migration at later time points of measurement. Moreover, TGFβ-primed UCMSCs secreted EVs that could upregulate the expression of chondrogenesis markers (<italic>COL2</italic> and <italic>ACAN</italic>) and downregulate fibrotic markers (<italic>COL1</italic> and <italic>RUNX2</italic>) in chondrocytes. Hence, priming UCMSCs with cytokines can deliver selective therapeutic effects of EV treatment in OA and chondrocyte-related disorders.</p>