circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models

Qilin Huang, Ziqiang Chu, Zihao Wang, Qiankun Li, Sheng Meng, Yao Lu, Kui Ma, Shengnan Cui, Wenzhi Hu, Wenhua Zhang, Qian Wei, Yanlin Qu, Haihong Li (), Xiaobing Fu () and Cuiping Zhang ()
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Qilin Huang: Tianjin Medical University
Ziqiang Chu: PLA General Hospital
Zihao Wang: PLA General Hospital
Qiankun Li: The First Medical Center, Chinese PLA General Hospital
Sheng Meng: PLA General Hospital
Yao Lu: The First Medical Center, Chinese PLA General Hospital
Kui Ma: PLA General Hospital
Shengnan Cui: PLA General Hospital
Wenzhi Hu: PLA General Hospital
Wenhua Zhang: PLA General Hospital
Qian Wei: PLA General Hospital
Yanlin Qu: PLA General Hospital
Haihong Li: the Seventh Affiliated Hospital of Sun Yat-sen University
Xiaobing Fu: PLA General Hospital
Cuiping Zhang: PLA General Hospital

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Date: 2024
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DOI: 10.1038/s41467-024-48284-3

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