Enhancement of wound healing by human multipotent stromal cell conditioned medium: The paracrine factors and p38 MAPK activation

Tu Lai Yew, Yeh Ting Hung, Hsin Yang Li, Hsin Wei Chen, Ling Lan Chen, Kuo Shu Tsai, Shih Hwa Chiou, Kuan Chong Chao, Tung Fu Huang, Hen Li Chen, Shih Chieh Hung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Wound healing can be improved by transplanting mesenchymal stem cells (MSCs). In this study, we have demonstrated the benefits of the conditioned medium derived from human MSCs (CM-MSC) in wound healing using an excisional wound model. CM-MSC accelerated wound closure with increased reepithelializ-ation, cell infiltration, granulation formation, and angiogenesis. Notably, CM-MSC enhanced epithelial and endothelial cell migration, suggesting the contribution of increased cell migration to wound healing enhanced by CM-MSC. Cytokine array, ELISA analysis, and quantitative RT-PCR revealed high levels of IL-6 in CM-MSC. Moreover, IL-6 added to the preconditioned medium enhanced both cell migration and wound healing, and antibodies against IL-6 blocked the increase in cell motility and wound closure by CM-MSC. The IL-6 secretory pathway of MSCs was inhibited by SB203580, an inhibitor of p38 MAPK or siRNA against p38 MAPK, suggesting IL-6 secretion by MSCs is mediated through the activation of p38 MAPK. Inactivation of p38 MAPK also reduced the expression and production of IL-8 and CXCL1 by MSCs, both of which were also demonstrated to enhance cell migration and wound closure. Thus, our data suggest MSCs promote wound healing through releasing a repertoire of paracrine factors via activation of p38 MAPK, and the CM-MSC may be applied to enhance wound healing.

Original languageEnglish
Pages (from-to)693-706
Number of pages14
JournalCell Transplantation
Volume20
Issue number5
DOIs
StatePublished - 2011

Keywords

  • Conditioned medium
  • Mesenchymal stem cells (MSCs)
  • P38 MAPK
  • Paracrine factors
  • Wound healing

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