期刊
STEM CELLS
卷 33, 期 7, 页码 2158-2168出版社
OXFORD UNIV PRESS
DOI: 10.1002/stem.1771
关键词
Exosomes; Mesenchymal stem cells; Wound healing; Wnt4; beta-Catenin; AKT
资金
- Major Research Plan of the National Natural Science Foundation of China [91129718]
- National Natural Science Foundation of China [31340040, 81272481, 81270214]
- Jiangsu Province for Outstanding Sci-tech Innovation Team in Colleges and Universities [SJK2013-10]
- Jiangsu Province's Outstanding Medical Academic Leader and Sci-tech Innovation Team Program [LJ201117]
- Jiangsu Province Doctoral Innovation Fund [CXZZ13_0703]
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 -catenin nuclear translocation and activity to enhance proliferation and migration of skin cells, which could be reversed by -catenin inhibitor ICG001. In vivo studies confirmed that the activation of Wnt/-catenin by hucMSC-Ex played a key role in wound re-epithelialization and cell proliferation. Furthermore, knockdown of Wnt4 in hucMSC-Ex abrogated -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
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