Efficacy of topical and systemic transplantation of mesenchymal stem cells in a rat model of diabetic ischemic wounds

Stem Cell Research & Therapy

Xiaojia Chen¹  Chengzhi Li²  Jiaji Liang³  Guanghui Xie³  Hongwei Liu³  Mariya M. El Akkawi³  Yingxuan Cao³  Xuan Liao³  Jianxin Yan³  Kecheng Li³ 

[1] Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, 510632, Guangzhou, People’s Republic of China;Guangdong Province Key Laboratory of Bioengineering Medicine, 510632, Guangzhou, People’s Republic of China;Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center, 510632, Guangzhou, People’s Republic of China;National Engineering Research Center of Genetic Medicine, 510632, Guangzhou, People’s Republic of China;Department of Interventional Radiology and Vascular Surgery, The First Affiliated Hospital of Jinan University, 510630, Guangzhou, People’s Republic of China;Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, 510630, Guangzhou, People’s Republic of China;Innovative Technology Research Institute of Plastic Surgery, 510630, Guangzhou, People’s Republic of China;Key Laboratory of Regenerative Medicine, Ministry of Education, 510632, Guangzhou, People’s Republic of China;

关键词: Bone marrow-derived mesenchymal stem cells;    Type 2 diabetes mellitus;    Critical limb ischemia;    Diabetic foot ulcers;    Chronic wounds;   

DOI  :  10.1186/s13287-021-02288-8

来源: Springer

【 摘 要 】

BackgroundMesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms.MethodA diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis.ResultBoth topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway.ConclusionsThe results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.

【 授权许可】

CC BY