Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis

Journal of Nanobiotechnology

Lang Chen¹  Yuan Xiong¹  Liangcong Hu¹  Guohui Liu¹  Ranyang Tao¹  Bobin Mi¹  Yiqiang Hu¹  Chenchen Yan¹  Ze Lin¹  Hang Xue¹  Xudong Xie¹  Adriana C. Panayi² 

[1] Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, 430022, Wuhan, China;Department of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 02215, Boston, MA, USA;

关键词: Exosomes;    Mesenchymal stem cells;    Pioglitazone;    Diabetic wound;    Angiogenesis;   

DOI  :  10.1186/s12951-021-00894-5

来源: Springer

【 摘 要 】

BackgroundEnhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing.ResultsWe isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing.ConclusionsPGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing.Graphic abstract

【 授权许可】

CC BY