Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis.

Jianing Ding,Bi Chen,Xin Wang,Jieyuan Zhang,Jianguang Xu

doi:10.1155/2019/9742765

Abstract

The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays involving cell proliferation, scratch wound healing, and tube formation. To test the effects in vivo, streptozotocin-induced diabetic rats were established. Two weeks after the procedure, histological analysis was used to measure wound-healing effects, and the neovascularization was evaluated as well. Our findings demonstrated that DFO-Exos activate the PI3K/AKT signaling pathway via miR-126 mediated PTEN downregulation to stimulate angiogenesis in vitro. This contributed to enhanced wound healing and angiogenesis in streptozotocin-induced diabetic rats in vivo. Our results suggest that, in cell-free therapies, exosomes derived from DFO preconditioned stem cells manifest increased proangiogenic ability.

Highlights

Diabetes mellitus has seen an increased incidence but the complications associated with this condition have increased in severity [1]
Wound healing depends on an important process of angiogenesis that is involved in delivering nutrition and oxygen to sites of wounds allowing for the proliferation of fibroblasts, synthesis of collagen, and reepithelialization [3]
The number of overall (Figure 4(b)) as well as mature blood vessels (Figure 4(c)) in the wound sites that received DFO-Exos and Exos treatment was enhanced remarkably compared to that in the control group, and a larger number of these two parameters were identified in the DFO-Exos group, when compared to that in Exos group (Figures 4(c) and 4(d)). These results revealed that DFO pretreatment enhances bone marrowderived MSCs (BMSCs)-derived exosomes mediated angiogenesis in wound healing

Summary

Introduction

Diabetes mellitus has seen an increased incidence but the complications associated with this condition have increased in severity [1]. A ubiquitous and incapacitating impediment in diabetes is decreased diabetic wound healing. This is a medical stumbling block of today that is relevant to patients who either have feet ulcers or are recuperating from complex surgeries that have a possibility of impeding regular activity, chronic ischemic skin lesions, and possible limb amputation of limbs [2]. Gets extended in diabetic patients due to weakened angiogenesis [4]. Diverse biological agents, such as different platelet concentrates, have determined their potential to improve the angiogenesis both in vivo and in vitro [5]. In order to hasten the process of healing diabetic wounds, the use of new approaches that supplement the local angiogenesis looks promising

Methods

Results

Conclusion