title: HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing.
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.
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Bin
authors: B
authors: Zhang
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Mei
authors: M
authors: Wang
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Aihua
authors: A
authors: Gong
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Xu
authors: X
authors: Zhang
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Xiaodan
authors: X
authors: Wu
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Yanhua
authors: Y
authors: Zhu
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Hui
authors: H
authors: Shi
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Lijun
authors: L
authors: Wu
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Wei
authors: W
authors: Zhu
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Hui
authors: H
authors: Qian
authors: Key Laboratory of Laboratory Medicine of Jiangsu Province, Medical School, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.|The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Wenrong
authors: W
authors: Xu
mesh_terms: D000818:Animals; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D012867:Skin / Q000293:injuries*; D060528:Wnt4 Protein / Q000235:genetics* / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D060528:Wnt4 Protein; C555583:Wnt4 protein, rat
keywords: AKT; Exosomes; Mesenchymal stem cells; Wnt4; Wound healing; β-Catenin