HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing

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ID: 307501
2014
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Abstract
Abstract Mesenchymal stem cell-derived exosomes (MSC-Ex) play important roles in tissue injury repair, however, the roles of MSC-Ex in skin damage repair and its mechanisms are largely unknown. Herein, we examined the benefit of human umbilical cord MSC-derived exosome (hucMSC-Ex) in cutaneous wound healing using a rat skin burn model. We found that hucMSC-Ex-treated wounds exhibited significantly accelerated re-epithelialization, with increased expression of CK19, PCNA, collagen I (compared to collagen III) in vivo. HucMSC-Ex promoted proliferation and inhibited apoptosis of skin cells after heat-stress in vitro. We also discovered that Wnt4 was contained in hucMSC-Ex, and hucMSC-Ex-derived Wnt4 promoted β-catenin nuclear translocation and activity to enhance proliferation and migration of skin cells, which could be reversed by β-catenin inhibitor ICG001. In vivo studies confirmed that the activation of Wnt/β-catenin by hucMSC-Ex played a key role in wound re-epithelialization and cell proliferation. Furthermore, knockdown of Wnt4 in hucMSC-Ex abrogated β-catenin activation and skin cell proliferation and migration in vitro. The in vivo therapeutic effects were also inhibited when the expression of Wnt4 in hucMSC-Ex was interfered. In addition, the activation of AKT pathway by hucMSC-Ex was associated with the reduction of heat stress-induced apoptosis in rat skin burn model. Collectively, our findings indicate that exosome-delivered Wnt4 provides new aspects for the therapeutic strategy of MSCs in cutaneous wound healing. Stem Cells 2015;33:2158–2168
Reference Key
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Authors Bin Zhang, Mei Wang, Aihua Gong, Xu Zhang, Xiaodan Wu, Yanhua Zhu, Hui Shi, Lijun Wu, Wei Zhu, Hui Qian, Wenrong Xu
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Journal stem cells international
Year 2014
DOI
10.1002/stem.1771
URL
https://academic.oup.com/stmcls/article-pdf/33/7/2158/42017345/stmcls_33_7_2158.pdf
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