CD93 hematopoietic stem cells improve diabetic wound healing by VEGF activation and downregulation of DAPK-1.

Diabetes is associated with numerous complications, such as diabetic skin wounds or ulcerations. The aim of this study was to evaluate experimentally the effectiveness of applying polycaprolactone (PCL)-gelatin scaffold, with or without rat CD93 hematopoietic stem cells (HSCs), in diabetic wound healing in a rat model. CD93 HSCs were aseptically isolated from rat bone marrow using fluorescent activated cell sorting (FACS) method and FACS-SORTER. A total of 25 Wistar rats were divided into five groups including Group I (sham, nondiabetic, and wound covered only with sterile dressing), II (control, diabetic rat), III (CD93 HSCs alone), IV (PCL-gelatin scaffold), and V (CD93 HSCs+PCL-gelatin scaffold). Animals were killed on Days 7, 14, or 28 posttreatment and histological sections were blindly evaluated by two expert pathologists. Death-associated protein kinase 1 (DAPK-1) gene and vesicular endothelial growth factors (VEGF) protein expression were evaluated using reverse transcription-polymerase chain reaction and western blot, respectively. The thickest and the thinnest epidermises microscopically were belonged to CD93+HSCs+scaffold and the control group, respectively. The growth rate of the epidermis and adnexal epithelia was the highest in both the cell and cell+scaffold groups. Evaluation of the protein expression level of VEGF indicated that the expression levels of this growth factor were the most on Day 7 posttreatment in sham, HSCs alone, and HSCs cell+scaffold groups. While the lowest expression levels of this growth factor was detected in the control and scaffold groups. The gene expression level of DAPK-1 on Day 7 posttreatment was higher than that of the Day 14 posttreatment in all groups. The highest and lowest gene expression levels of DAPK-1 belonged to control and sham groups, respectively. According to our findings, CD93 HSCs offer new prospects for the treatment of diabetic ulcers and concomitant application of these cells with PCL-gelatin nanofiber scaffold significantly improves diabetic wound treatment.