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

Author:

Zhu Mengting12,Chu Yunpeng1,Shang Qianwen1,Zheng Zhiyuan1,Li Yanan12,Cao Lijuan1,Chen Yongjing1,Cao Jianchang3,Lee Oscar K.4,Wang Ying3,Melino Gerry2,Lv Guozhong5,Shao Changshun6,Shi Yufang13

Affiliation:

1. The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine Soochow University Medical College, Suzhou, People’s Republic of China

2. Department of Experimental Medicine and Biochemical Sciences University of Rome ‘Tor Vergata’, Rome, Italy

3. CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Shanghai, People’s Republic of China

4. Institute for Tissue Engineering and Regenerative Medicine The Chinese University of Hong Kong, HongKong, People’s Republic of China

5. Department of Burn Surgery The 3rd People’s Hospital of Wuxi and Wuxi Medical College of Jiangnan University, Wuxi, People’s Republic of China

6. State Key Laboratory of Radiation Medicine and Protection Institutes for Translational Medicine, Soochow University, Suzhou, People’s Republic of China

Abstract

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.

Funder

State Key Laboratory of Radiation Medicine and Protection, Soochow University

Better Society Program of Jiangsu Province

Suzhou Science and Technology Program

National Natural Science Foundation of China

National Key R&D Program of China

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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