Mesenchymal stromal cells pretreated with pro-inflammatory cytokines promote skin wound healing through VEGFC-mediated angiogenesis.,STEM CELLS Translational Medicine

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Mesenchymal stromal cells pretreated with pro-inflammatory cytokines promote skin wound healing through VEGFC-mediated angiogenesis.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-06-13 , DOI: 10.1002/sctm.19-0241
Mengting Zhu _{1,

2} , Yunpeng Chu ₁ , Qianwen Shang ₁ , Zhiyuan Zheng ₁ , Yanan Li _{1,

2} , Lijuan Cao ₁ , Yongjing Chen ₁ , Jianchang Cao ₃ , Oscar K Lee ₄ , Ying Wang ₃ , Gerry Melino ₂ , Guozhong Lv ₅ , Changshun Shao ₆ , Yufang Shi _{1,

3}

Affiliation

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.

中文翻译：

用促炎细胞因子预处理的间充质基质细胞通过 VEGFC 介导的血管生成促进皮肤伤口愈合。

皮肤是人体最大的器官。皮肤伤口是最常见的伤口形式之一。间充质基质细胞 (MSC) 已被用于通过其旁分泌因子帮助皮肤伤口愈合。由于用 IFN-γ 和 TNF-α (IT) 处理可以极大地富集和扩增 MSCs 的分泌组，我们在这里测试了来自用 IT 预处理的 MSCs 的上清液，称为 S-MSCs-IT，是否具有改善的伤口愈合效果通过使用小鼠皮肤切除模型，发现 S-MSCs-IT 在皮肤伤口愈合过程中比对照上清液 (S-MSCs) 在促进血管生成、收缩胶原沉积和加速伤口闭合方面更有效。VEGFC 而非 VEGFA 被 IT 显着上调，并被发现是介导 S-MSCs-IT 改善伤口愈合效果的关键因素。我们的结果表明，可以通过用炎性细胞因子预处理来增强 MSCs 对伤口愈合的有益旁分泌作用。IT 治疗可能代表了一种优化 MSCs 对皮肤损伤治疗效果的新策略。

更新日期：2020-06-13

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