CD93 Hematopoietic Stem Cells (HSCs) Improve Diabetic Wound Healing by VEGF Activation and downregulation of DAPK-1

Introduction: Diabetes is associated with numerous complications, such as diabetic skin wounds or ulcerations. The aim of this study was to experimentally evaluate the effectiveness of applying PCL-gelatin scaffold, with or without rat CD93 hematopoietic stem cells (HSCs), in diabetic wound healing in a rat model.Material and method: CD93 HSCs were ascetically isolated from rat bone marrow using FACS method and FACS-SORTER. A total of 25 Wistar rats were divided into five groups including: group I (sham, non-diabetic and wound covered only with sterile dressing), group II (control, diabetic rat), III (CD93 HSCs alone), IV (PCL-gelatin scaffold), and V (CD93 HSCs+PCL-gelatin scaffold). Animals were sacrificed on days 7,14, or 28 post-treatment and histological sections were blindly evaluated by two expert pathologists. Death-associated protein kinase (DAPK) 1 gene and vesicular endothelia growth factors (VEGF) protein expression were evaluated using RT-PCR and western blot, respectively. Finding and Conclusions: The thickest and the thinnest epidermises microscopically were belonged to CD93+HSCs+scaffold and the control group, respectively. The growth rate of 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 was the highest on day 7 post-treatment in the 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 post-treatment was higher than that of day 14post-treatment in all the groups. The highest and lowest gene expression levels of DAPK-1 belonged to the 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.

کلیدواژه ها:

Wound Healing ، hematopoietic stem cells ، CD93 ، PCL-gelatin scaffold