title: Transdifferentiation of Umbilical Cord-Derived Mesenchymal Stem Cells Into Epidermal-Like Cells by the Mimicking Skin Microenvironment.
abstract: Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are multipotent, primitive, and have been widely used for skin tissue engineering. Their transdifferentiation is determined by the local microenvironment. In this study, we investigated the potential epidermal differentiation of UC-MSCs and the formation of epidermis substitutes in a 3-dimensional (3D) microenvironment, which was fabricated by UC-MSCs embedded into collagen-chitosan scaffolds (CCSs) combined with an air-liquid interface (ALI) culture system. Using fluorescence microscope, we observed that UC-MSCs were spindle-shaped and evenly distributed in the scaffold. Methyl thiazolyl blue tetrazolium bromide assay and Live/Dead assay indicated that the CCSs have good biocompatibility with UC-MSCs. Immunohistochemistry and western blotting assay showed that UC-MSCs on the surface of the CCSs were positive for the epidermal markers cytokeratin 19 and involucrin at 14 days. In addition, hematoxylin-eosin staining indicated that multilayered epidermis substitutes were established. The constructed epidermis substitutes were applied to treat full-thickness wounds in rats and proved to promote wound healing. In conclusion, manipulating the 3D microenvironment is a novel method for inducing the epidermal differentiation of MSCs to engineer epidermal substitutes, which provides an alternative strategy for skin tissue engineering.
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Deyun
authors.initials: D
authors.lastname: Chen
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Hao
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Tong
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ti
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Hou
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Liu
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.affiliation: Chinese PLA General Hospital, Beijing, China fuxiaobing@vip.sina.com hanwdrsw@sina.com.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage; D004195:Disease Models, Animal; D004817:Epidermis / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries* / Q000473:pathology; D023822:Tissue Engineering / Q000379:methods*; D014470:Umbilical Cord / Q000648:ultrastructure*; D014945:Wound Healing; D014947:Wounds and Injuries / Q000473:pathology / Q000628:therapy*
chemical_list: D004247:DNA
keywords: air–liquid interface; collagen–chitosan scaffold; epidermal-like cells; human umbilical cord–derived mesenchymal stem cells; wound healing