Human Umbilical Cord Mesenchymal Stem Cells Transplantation Promotes Cutaneous Wound Healing of Severe Burned Rats

Lingying Liu,Hongjie Duan,Jundong Du,Quan Hu,Yonghui Yu,Yusen Hou,Wanli Chu,Haijun Zhang,Jiake Chai,Dimas Tadeu Covas

doi:10.1371/journal.pone.0088348

Lingying Liu, Hongjie Duan + Show 8 more

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https://doi.org/10.1371/journal.pone.0088348

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Abstract

BackgroundSevere burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC) therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs) could on wound healing in a rat model of severe burn and its potential mechanism.MethodsAdult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI), and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA.ResultsWe found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation.ConclusionThe study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas.

Highlights

Severe burns are one of dangerous surgical emergency
At week 11 after hUC-mesenchymal stem cell (MSC) transplantation, the wound epithelium of 5 of 6 rats had recovered in the human umbilical cord MSCs (hUCMSCs) group, whereas all 6 rats in the burn group displayed a lack of healing at the same time (Fig. 1A)
We further investigated the level of VEGF in the cutaneous wounds to determine the possible effect of hUC-MSCs on wound angiogenesis

Summary

Introduction

Severe burns are one of dangerous surgical emergency. The key step for rescuing severe burn patients is to cover the wounds as early as possible [1]. Using xenogenic pig skin is usually subjected to antigen rejection reactions and infection risk. Novel and effective therapies for promoting wound healing of severe burn patients are needed. Severe burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC) therapy contributes to facilitate wound healing. We investigated effect of human umbilical cord MSCs (hUC-MSCs) could on wound healing in a rat model of severe burn and its potential mechanism

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