Abstract

Endothelial progenitor cells (EPCs) are involved in the neovascularization in traumatic and ischemic sites, but EPCs are “detained” in bone marrow under diabetic conditions, which results in reduction of the number of EPCs and their biological activity in peripheral blood. Based on our previous study to mobilize autologous bone marrow EPCs by administering AMD3100+G-CSF to realize the optimal effect, our present study is aimed at exploring the effects of transplanting EPCs locally in a wound model of diabetic mice. First, we prepared and identified EPCs, and the biological functions and molecular characteristics were compared between EPCs from DB/+ and DB/DB mice. Then, we performed full-thickness skin resection in DB/DB mice and tested the effect of local transplantation of EPCs on skin wound healing. The wound healing process was recorded using digital photographs. The animals were sacrificed on postoperative days 7, 14, and 17 for histological and molecular analysis. Our results showed that DB/+ EPCs were biologically more active than those of DB/DB EPCs. When compared with the control group, local transplantation of EPCs accelerated wound healing in DB/DB mice by promoting wound granulation tissue formation, angiogenesis, and collagen fiber deposition, but there was no significant difference in wound healing between DB/+ EPCs and DB/DB EPCs transplanted into the wound. Furthermore, local transplantation of EPCs promoted the expression of SDF-1, CXCR4, and VEGF. We speculated that EPC transplantation may promote wound healing through the SDF-1/CXCR4 axis. This point is worth exploring further. Present data are of considerable significance because they raise the possibility of promoting wound healing by isolating autologous EPCs from the patient, which provides a new approach for the clinical treatment of diabetic wounds in the future.

Highlights

  • Diabetes is a common endocrine disease, and approximately 20% of patients develop diabetic wounds, with leg or foot ulcers being the most common [1]

  • Since our study is aimed at exploring the effect of Endothelial progenitor cells (EPCs) transplantation on wound healing, we first attempted to isolate and identify EPCs

  • To explore the functions of EPCs in wound healing, we examined biological functions of EPCs and three important factors related to their function: SDF1, VEGF, and CXCR4

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Summary

Introduction

Diabetes is a common endocrine disease, and approximately 20% of patients develop diabetic wounds, with leg or foot ulcers being the most common [1]. The decrease in the ability to metabolize glucose in patients can cause hyperglycemia, which seriously affects the process of wound repair [2]. Based on WHO epidemiological projections, diabetes will become the seventh leading cause of death by 2030. More than 80% of diabetes deaths will occur in low- and middle-income countries [1,2,3], while approximately 50%-70% of amputations are due to diabetes trauma. It has been reported that leg amputation occurs every 30 seconds due to diabetes trauma worldwide [4]

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