Mesenchymal stromal cells pretreated with pro-inflammatory cytokines promote skin wound healing through VEGFC-mediated angiogenesis

Mengting Zhu, Yunpeng Chu, Qianwen Shang, Zhiyuan Zheng, Yanan Li, Lijuan Cao, Yongjing Chen, Jianchang Cao, Oscar K. Lee, Ying Wang, Gerry Melino, Guozhong Lv, Changshun Shao, Yufang Shi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Skin is the largest organ of the human body. Skin wound is one of the most common forms of wound. Mesenchymal stromal cells (MSCs) have been used to aid skin wound healing via their paracrine factors. Because the secretome of MSCs can be greatly enriched and amplified by treatment with IFN-γ and TNF-α (IT), we here tested whether supernatant derived from MSCs pretreated with IT, designated as S-MSCs-IT, possesses improved wound healing effect by using a murine model of cutaneous excision, S-MSCs-IT was found to be more potent in promoting angiogenesis, constricting collagen deposition and accelerating wound closure than control supernatant (S-MSCs) during the healing of skin wound. VEGFC, but not VEGFA, was greatly upregulated by IT and was found to be a key factor in mediating the improved wound healing effect of S-MSCs-IT. Our results indicate that the beneficial paracrine effect of MSCs on wound healing can be enhanced by pretreatment with inflammatory cytokines. IT treatment may represent a new strategy for optimizing the therapeutic effect of MSCs on skin injuries.

Original languageEnglish (US)
Pages (from-to)1218-1232
Number of pages15
JournalStem Cells Translational Medicine
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2020

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

Keywords

  • IFN-γ
  • TNF-α
  • VEGFC
  • angiogenesis
  • mesenchymal stromal cells
  • wound healing

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