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

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

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.
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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