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Stem Cells. 2015 Jul;33(7):2158-68. doi: 10.1002/stem.1771. Epub 2015 May 13.

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

Author information

1
Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
2
The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.

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.

KEYWORDS:

AKT; Exosomes; Mesenchymal stem cells; Wnt4; Wound healing; β-Catenin

PMID:
24964196
DOI:
10.1002/stem.1771
[Indexed for MEDLINE]
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