PMID- 30546011 OWN - NLM STAT- MEDLINE DCOM- 20190122 LR - 20200309 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 9 IP - 1 DP - 2018 Dec 13 TI - Tissue engineering of human hair follicles using a biomimetic developmental approach. PG - 5301 LID - 10.1038/s41467-018-07579-y [doi] LID - 5301 AB - Human skin constructs (HSCs) have the potential to provide an effective therapy for patients with significant skin injuries and to enable human-relevant drug screening for skin diseases; however, the incorporation of engineered skin appendages, such as hair follicles (HFs), into HSCs remains a major challenge. Here, we demonstrate a biomimetic approach for generation of human HFs within HSCs by recapitulating the physiological 3D organization of cells in the HF microenvironment using 3D-printed molds. Overexpression of Lef-1 in dermal papilla cells (DPC) restores the intact DPC transcriptional signature and significantly enhances the efficiency of HF differentiation in HSCs. Furthermore, vascularization of hair-bearing HSCs prior to engraftment allows for efficient human hair growth in immunodeficient mice. The ability to regenerate an entire HF from cultured human cells will have a transformative impact on the medical management of different types of alopecia, as well as chronic wounds, which represent major unmet medical needs. FAU - Abaci, Hasan Erbil AU - Abaci HE AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. FAU - Coffman, Abigail AU - Coffman A AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. FAU - Doucet, Yanne AU - Doucet Y AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. FAU - Chen, James AU - Chen J AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. AD - Department of Systems Biology, Columbia University Medical Center, New York, NY, 10032, USA. FAU - Jackow, Joanna AU - Jackow J AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. FAU - Wang, Etienne AU - Wang E AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. FAU - Guo, Zongyou AU - Guo Z AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. FAU - Shin, Jung U AU - Shin JU AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. FAU - Jahoda, Colin A AU - Jahoda CA AD - Department of Biosciences, Durham University, Durham, UK. FAU - Christiano, Angela M AU - Christiano AM AD - Department of Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. amc65@cumc.columbia.edu. AD - Department of Genetics and Development, Columbia University Medical Center, New York, NY, 10032, USA. amc65@cumc.columbia.edu. LA - eng GR - K01 AR072131/AR/NIAMS NIH HHS/United States GR - P30 AR069632/AR/NIAMS NIH HHS/United States GR - UH2 EB017103/EB/NIBIB NIH HHS/United States GR - UL1 TR001873/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20181213 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (LEF1 protein, human) RN - 0 (Lymphoid Enhancer-Binding Factor 1) SB - IM MH - Alopecia/pathology/*therapy MH - Animals MH - Biomimetics MH - Cell Differentiation MH - Cells, Cultured MH - Dermis/*cytology MH - Hair Follicle/cytology/*growth & development/*transplantation MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Lymphoid Enhancer-Binding Factor 1/biosynthesis MH - Male MH - Mice MH - Mice, Nude MH - Tissue Engineering/*methods MH - Transplantation, Heterologous PMC - PMC6294003 COIS- A.M.C. and C.A.J. are founders of Rapunzel Bioscience Inc, focused on developing regenerative therapies for skin and hair disorders. The remaining authors declare no competing interests. EDAT- 2018/12/14 06:00 MHDA- 2019/01/23 06:00 PMCR- 2018/12/13 CRDT- 2018/12/15 06:00 PHST- 2018/05/29 00:00 [received] PHST- 2018/10/25 00:00 [accepted] PHST- 2018/12/15 06:00 [entrez] PHST- 2018/12/14 06:00 [pubmed] PHST- 2019/01/23 06:00 [medline] PHST- 2018/12/13 00:00 [pmc-release] AID - 10.1038/s41467-018-07579-y [pii] AID - 7579 [pii] AID - 10.1038/s41467-018-07579-y [doi] PST - epublish SO - Nat Commun. 2018 Dec 13;9(1):5301. doi: 10.1038/s41467-018-07579-y.