Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF‐1α pathway by improving the blood preservation solution

Abstract

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF‐1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF‐1α pathway were determined by measuring expression of VEGF, EGF, HIF‐1α, and HSP‐90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF‐1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α‐SMA in skin tissues, and reduced TNF‐α, IL‐1β, and IL‐6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF‐1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF‐1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF‐1α pathway.

Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases

“…Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing ( Zhu et al, 2020 ). Olson et al (2019) reported improvements in wound healing by evaluating the wound area, volume and depth in daprodustat topical formulation-treated healthy volunteers with intact skin and diabetic foot ulcer patients and the mechanism was illustrated by activation of HIF-1 signaling and promoted vascularization.…”