Frontiers in Immunology (Oct 2022)

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

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

DOI
https://doi.org/10.3389/fimmu.2022.1041592
Journal volume & issue
Vol. 13

Abstract

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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 (COL2 and ACAN) and downregulate fibrotic markers (COL1 and RUNX2) in chondrocytes. Hence, priming UCMSCs with cytokines can deliver selective therapeutic effects of EV treatment in OA and chondrocyte-related disorders.

Keywords