Enhancement of Bone-Marrow-Derived Mesenchymal Stem Cell Angiogenic Capacity by NPWT for a Combinatorial Therapy to Promote Wound Healing with Large Defect.

Kangquan Shou,Xiang Hu,Xun Zheng,Aixi Yu,Yahui Niu,Zhanjun Ma,Chao Jian,Baiwen Qi

doi:10.1155/2017/7920265

Abstract

Poor viability of engrafted bone marrow mesenchymal stem cells (BMSCs) often hinders their application for wound healing, and the strategy of how to take full advantage of their angiogenic capacity within wounds still remains unclear. Negative pressure wound therapy (NPWT) has been demonstrated to be effective for enhancing wound healing, especially for the promotion of angiogenesis within wounds. Here we utilized combinatory strategy using the transplantation of BMSCs and NPWT to investigate whether this combinatory therapy could accelerate angiogenesis in wounds. In vitro, after 9-day culture, BMSCs proliferation significantly increased in NPWT group. Furthermore, NPWT induced their differentiation into the angiogenic related cells, which are indispensable for wound angiogenesis. In vivo, rat full-thickness cutaneous wounds treated with BMSCs combined with NPWT exhibited better viability of the cells and enhanced angiogenesis and maturation of functional blood vessels than did local BMSC injection or NPWT alone. Expression of angiogenesis markers (NG2, VEGF, CD31, and α-SMA) was upregulated in wounds treated with combined BMSCs with NPWT. Our data suggest that NPWT may act as an inductive role to enhance BMSCs angiogenic capacity and this combinatorial therapy may serve as a simple but efficient clinical solution for complex wounds with large defects.

Highlights

The healing of large areas of full-thickness skin defects is a challenging clinical problem [1, 2]
bone marrow mesenchymal stem cells (BMSCs) cultured under Negative pressure wound therapy (NPWT) maintained well viability for up to 9 days (Figures 2(c) and 2(e))
Our results demonstrated for the first time that BMSC + NPWT could significantly promote cutaneous wound healing, characterized by robust and enhanced vascularization at wound sites

Summary

Introduction

The healing of large areas of full-thickness skin defects is a challenging clinical problem [1, 2]. Optimum healing of a cutaneous wound requires an effective way to stimulate rapid angiogenesis because blood vessels are crucial for wound repair for delivering oxygen and nutrients to the host cells in the wounds [3]. Mesenchymal stem cells have been shown to play an important role in the healing of cutaneous wounds [5]. After the dermal wounding, endogenous mesenchymal stem cells (MSC) will be mobilized into the circulation, homing into the wounded skin and eventually differentiating into skin cells [6]. Extremity ischemia is a powerful stimulant for marrow stem cell recruitment, fewer progenitor cells were able to migrate to the ischemic wound [7]. The poor viability and low levels of BMSCs engraftment often limit their therapeutic potential [9]

Methods

Results

Discussion

Conclusion