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

  • ACS Nano. 2023 Jul 13. doi: 10.1021/acsnano.3c01612.
Hongfu Cao ,  Manyu Chen ,  Xiaolin Cui  1  2 ,  Yuan Liu ,  Yuhan Liu  3 ,  Siyan Deng ,  Tun Yuan  4 ,  Yujiang Fan ,  Qiguang Wang ,  Xingdong Zhang
Affiliations
  • 1. School of Medicine, the Chinese University of Hong Kong, Shenzhen 518172, China.
  • 2. Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopedic Surgery & Musculoskeletal Medicine, Centre for Bioengineering & Nanomedicine, University of Otago, Christchurch 8011, New Zealand.
  • 3. Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
  • 4. Sichuan Testing Center for Biomaterials and Medical Devices Co. Ltd, 29 Wangjiang Road, Chengdu, Sichuan 610065, China.
PMID: 37439514 DOI: 10.1021/acsnano.3c01612
Abstract

As chondrocytes from osteoarthritic cartilage usually exhibit aging and senescent characteristics, targeting aging chondrocytes could be a potential therapeutic strategy. In this study, exosomes derived from umbilical cord-derived mesenchymal stem cells (UCMSC-EXOs) combined with the chondrocyte-targeting capacity and controlled-release system were proposed for osteoarthritis (OA) treatment via rejuvenating aging chondrocytes. The essential functional miRNAs within UCMSC-EXOs were investigated, with the p53 signaling pathway identified as the key factor. To improve the therapeutic efficiency and retention time of UCMSC-EXOs in vivo, the exosomes (EXOs) were engineered on membranes with a designed chondrocyte-targeting Polymers, and encapsulated within thiolated hyaluronic acid microgels to form a "two-phase" releasing system, which synergistically facilitated the repair of OA cartilage in a rat model. Together, this study highlighted the rejuvenating effects of UCMSC-EXOs on OA chondrocytes and the potential to combine with chondrocyte-targeting and sustained-release strategies toward a future cell-free OA treatment.

Keywords
Osteoarthritis; chondrocyte-targeting; senescence; sustained-release; umbilical cord-derived mesenchymal stem cells-derived exosomes.
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