title: Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors.
abstract: : Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity.
  
  
  
  In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.|Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.|Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, People's Republic of China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.|Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Cai
authors.affiliation: Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Jinmei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Clinical Research Center, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Yanpei
authors.initials: Y
authors.lastname: Cao
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.|Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Ge
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Tredget
authors.affiliation: Shenzhen Fuhua Aesthetic Hospital, Shenzhen, People's Republic of China.
authors.forename: Mengjun
authors.initials: M
authors.lastname: Cao
authors.affiliation: Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Beijing, People's Republic of China wu.yaojiong@sz.tsinghua.edu.cn.|Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Yaojiong
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000078404:Epidermal Cells; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008055:Lipids / Q000032:analysis; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D038081:Organogenesis / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects; D012627:Sebaceous Glands / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051153:Wnt Proteins / Q000494:pharmacology
chemical_list: D055415:Bone Morphogenetic Protein 4; D008055:Lipids; D051153:Wnt Proteins
keywords: BMP4; Epidermal stem cells; Hair follicle regeneration; Sebaceous glands; Skin-derived precursors