Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats

PLoS One. 2014 Feb 20;9(2):e88348. doi: 10.1371/journal.pone.0088348. eCollection 2014.

Abstract

Background: 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. 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.

Methods: Adult 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.

Results: We 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.

Conclusion: The 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burns / therapy*
  • Green Fluorescent Proteins
  • Humans
  • Laser-Doppler Flowmetry
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Polymerase Chain Reaction
  • Rats
  • Rats, Wistar
  • Umbilical Cord / cytology*
  • Wound Healing / physiology*

Substances

  • Green Fluorescent Proteins

Grant support

This work was supported by the National Natural Science Foundation of China (81372052), General Financial Grant from the China Postdoctoral Science Foundation (2013M532200), and the First Affiliated Hospital to the PLA General Hospital Science Research Foundation of China (QN201207). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.