title: Role of Keratinocyte Growth Factor in the Differentiation of Sweat Gland-Like Cells From Human Umbilical Cord-Derived Mesenchymal Stem Cells.
abstract: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have higher proliferation potency and lower immune resistance than human bone marrow MSCs and can differentiate into various functional cells. Many regulatory factors, including keratinocyte growth factor (KGF), are involved in the development of skin and cutaneous appendages. Although KGF is important in wound healing, the role of KGF in hUC-MSC differentiation remains unknown. In our previous work, we found the mixing medium (nine parts of basic sweat-gland [SG] medium plus one part of conditioned heat-shock SG medium) could induce hUC-MSC differentiation to sweat gland-like cells (SGCs). In this study, we further improved the inducing medium and determined the effects of KGF in hUC-MSC differentiation. We found KGF expression in the SGCs and that recombinant human KGF could induce hUC-MSC differentiation into SGCs, suggesting KGF plays a pivotal role in promoting hUC-MSC differentiation to SGCs. Furthermore, the SGCs differentiated from hUC-MSCs were applied to severely burned skin of the paw of an in vivo severe combined immunodeficiency mouse burn model. Burned paws treated with SGCs could regenerate functional sparse SGs 21 days after treatment; the untreated control paws could not. Collectively, these results demonstrated that KGF is a critical growth factor for SGC differentiation from hUC-MSCs and the differentiated SGCs from hUC-MSCs may have a potential therapeutic application for regeneration of destroyed SGs and injured skin.
  
  
  CONCLUSIONS
  There is growing evidence demonstrating a potential therapeutic application of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in injured skin. In the current study, conditioned media and chemically defined media with recombinant human keratinocyte growth factor (KGF) could induce hUC-MSC differentiation into sweat gland-like cells (SGCs). Moreover, the differentiated SGCs from hUC-MSCs could regenerate functional sparse sweat glands in a mouse burn model, which provides further insight into the mechanisms of the role of KGF and a potential therapeutic application of differentiated SGCs for regeneration of destroyed sweat glands and injured skin.
authors.affiliation: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China Institute of Emergency Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China Wound Healing and Cell Biology Laboratory, Burns Institute, First Affiliated Hospital (304th Hospital), General Hospital of PLA, Beijing, People's Republic of China Department of Surgery, State University of New York Upstate Medical University, Syracuse, New York, USA.
authors.forename: Yongan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China Institute of Emergency Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Yucai
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Mengyan
authors.initials: M
authors.lastname: Xu
authors.affiliation: Wound Healing and Cell Biology Laboratory, Burns Institute, First Affiliated Hospital (304th Hospital), General Hospital of PLA, Beijing, People's Republic of China.
authors.forename: Kui
authors.initials: K
authors.lastname: Ma
authors.affiliation: Wound Healing and Cell Biology Laboratory, Burns Institute, First Affiliated Hospital (304th Hospital), General Hospital of PLA, Beijing, People's Republic of China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China Institute of Emergency Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China zmhz@hotmail.com wangg@upstate.edu.
authors.forename: Mao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse, New York, USA zmhz@hotmail.com wangg@upstate.edu.
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism / Q000628:therapy; D002454:Cell Differentiation / Q000187:drug effects*; D005312:Fetal Blood / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism / Q000494:pharmacology*; D064593:Heterografts; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D012867:Skin / Q000378:metabolism; D013545:Sweat Glands / Q000166:cytology / Q000378:metabolism*
chemical_list: C496453:FGF7 protein, human; D051523:Fibroblast Growth Factor 7
keywords: Burns; Mesenchymal stem cell; Sweat gland; Tissue regeneration; Transdifferentiation; Umbilical cord; Wharton’s jelly