Engineered exosomes derived from miR-132-overexpresssing adipose stem cells promoted diabetic wound healing and skin reconstruction

Lifeng Ge; Kangyan Wang; Hang Lin; Endong Tao; Weijie Xia; Fulin Wang; Cong Mao; Yongzeng Feng

doi:10.3389/fbioe.2023.1129538

Engineered exosomes derived from miR-132-overexpresssing adipose stem cells promoted diabetic wound healing and skin reconstruction

Front Bioeng Biotechnol. 2023 Mar 1:11:1129538. doi: 10.3389/fbioe.2023.1129538. eCollection 2023.

Authors

Lifeng Ge^{1

2}, Kangyan Wang^{1

2}, Hang Lin^{1

2}, Endong Tao^{1

2}, Weijie Xia^{1

2}, Fulin Wang^{1

2}, Cong Mao^{1

2}, Yongzeng Feng^{1

2}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
² Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou Medical University, Wenzhou, China.

Abstract

The tissue reconstruction of diabetic wounds mainly depends on the proliferation and remodelling of cutaneous cells around wounds and the transplantation of random skin flaps, however, the proliferation of cells or survival of skin flaps are difficult due to the severe inflammation and other problems caused by diabetes. The stem cell-derived exosomes loaded with miRNA can be an effective therapeutic strategy for promoting diabetic wound healing. Therefore, in this study, the engineered exosomes derived from miR-132-overexpressing adipose stem cells (miR-132-exo) was obtained for promoting the healing of diabetic wounds and skin flaps. In vitro, the miR-132-exo promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). In vivo, streptozotocin (STZ) induced diabetic mice were used to create full-thickness skin wounds and random skin flaps to further investigate the healing effect of miR-132-exo. The results showed miR-132-exo evidently enhanced the survival of skin flaps and promote diabetic wound healing, through reducing local inflammation, promoting angiogenesis and stimulating M2-macrophages polarization mediated by NF-κB signaling pathway. These novel findings demonstrated that engineered miR-132-exo can be a potent therapeutic for treating diabetic wounds and inflammatory-related disease.

Keywords: diabetic wound; exosomes; inflammation; macrophages polarization; miR-132.

Grants and funding

This work was financially supported by the Zhejiang Provincial Natural Science Foundation of China (NO. Y19H060034) and Medical Health Science and Technology Project of Zhejiang Province (NO. 2020KY183) and National Undergraduate Training Programs for Innovation and Entrepreneurship (NO. 202110343034).