Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes

As chondrocytes from osteoarthritic cartilage usuallyexhibit agingand senescent characteristics, targeting aging chondrocytes couldbe a potential therapeutic strategy. In this study, exosomes derivedfrom umbilical cord-derived mesenchymal stem cells (UCMSC-EXOs) combinedwith the chondrocyte-targeting capacity and controlled-release systemwere proposed for osteoarthritis (OA) treatment via rejuvenating agingchondrocytes. The essential functional miRNAs within UCMSC-EXOs wereinvestigated, with the p53 signaling pathway identified as the keyfactor. To improve the therapeutic efficiency and retention time ofUCMSC-EXOs in vivo, the exosomes (EXOs) were engineeredon membranes with a designed chondrocyte-targeting polymers, and encapsulatedwithin thiolated hyaluronic acid microgels to form a two-phasereleasing system, which synergistically facilitated the repair ofOA cartilage in a rat model. Together, this study highlighted therejuvenating effects of UCMSC-EXOs on OA chondrocytes and the potentialto combine with chondrocyte-targeting and sustained-release strategiestoward a future cell-free OA treatment.

Automated summary

This study suggests that exosomes derived from umbilical cord-derived mesenchymal stem cells (UCMSC-EXOs) combined with chondrocyte-targeting capacity and controlled-release system have the potential for osteoarthritis (OA) treatment by rejuvenating aging chondrocytes. The research identified the essential miRNAs within UCMSC-EXOs and the p53 signaling pathway as a key factor. By engineering the exosomes on membranes and encapsulating them in hyaluronic acid microgels, a two-phase releasing system was formed, which synergistically facilitated the repair of OA cartilage in a rat model. Overall, this study highlights the rejuvenating effects of UCMSC-EXOs on OA chondrocytes and their potential for future cell-free OA treatment when combined with chondrocyte-targeting and sustained-release strategies.