2. Academic Validation
  3. Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis

Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis

  • J Nanobiotechnology. 2023 Sep 22;21(1):341. doi: 10.1186/s12951-023-02086-9.
Shu Zhao 1 2,  Guanghui Xiu 3,  Jian Wang 1,  Yi Wen 1,  Jinyuan Lu 4,  Baitong Wu 1,  Guangming Wang 1,  Danjing Yang 1,  Bin Ling 5,  Dajiang Du 6,  Jun Xu 7
Affiliations

Affiliations

  • 1 East Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China, 200120.
  • 2 Department of Plastic Surgery, Shanghai Fourth People's Hospital, School of Medicine,Tongji University, Shanghai, 200434, People's Republic of China.
  • 3 Department of Intensive Care Unit, Affiliated Hospital of Yunnan University (The Second People's Hospital of Yunnan Province), Yunnan University, Kunming, 650021, People's Republic of China.
  • 4 Department of Hematology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 5 Department of Intensive Care Unit, Affiliated Hospital of Yunnan University (The Second People's Hospital of Yunnan Province), Yunnan University, Kunming, 650021, People's Republic of China. ynshhyyicu@163.com.
  • 6 Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People's Republic of China. dudajiang@sjtu.edu.cn.
  • 7 East Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China, 200120. xunymc2000@yahoo.com.
PMID: 37736726 DOI: 10.1186/s12951-023-02086-9
Abstract

Osteoarthritis (OA) is a degenerative joint disease involving cartilage. Exosomes derived from Mesenchymal stem cells (MSCs) therapy improves articular cartilage repair, but subcutaneous fat (SC) stromal cells derived exosomes (MSCsSC-Exos), especially engineering MSCsSC-Exos for drug delivery have been rarely reported in OA therapy. This objective of this study was to clarify the underlying mechanism of MSCsSC-Exos on cartilage repair and therapy of engineering MSCsSC-Exos for drug delivery in OA. MSCsSC-Exos could ameliorate the pathological severity degree of cartilage via miR-199a-3p, a novel molecular highly enriched in MSCsSC-Exos, which could mediate the mTOR-autophagy pathway in OA rat model. Intra-articular injection of antagomiR-199a-3p dramatically attenuated the protective effect of MSCsSC-Exos-mediated on articular cartilage in vivo. Furthermore, to achieve the superior therapeutic effects of MSCsSC-Exos on injured cartilage, engineering exosomes derived from MSCsSC as the chondrocyte-targeting miR-199a-3p delivery vehicles were investigated in vitro and in vivo. The chondrocyte-binding peptide (CAP) binding MSCsSC-Exos could particularly deliver miR-199a-3p into the chondrocytes in vitro and into deep articular tissues in vivo, then exert the excellent protective effect on injured cartilage in DMM-induced OA mice. As it is feasible to obtain human subcutaneous fat from healthy donors by liposuction operation in clinic, meanwhile engineering MSCsSC-Exos to realize targeted delivery of miR-199a-3p into chondrocytes exerted excellent therapeutic effects in OA animal model in vivo. Through combining MSCsSC-Exos therapy and miRNA therapy via an engineering approach, we develop an efficient MSCsSC-Exos-based strategy for OA therapy and promote the application of targeted-MSCsSC-Exos for drug delivery in the future.

Keywords

Autophagy; Cartilage-targeted; Engineering exosomes; Osteoarthritis; miR-199a-3p.

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