期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07579-y
关键词
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资金
- National Center for Advancing Sciences at the National Institutes of Health [NCATS: 5UH2EB017103-05]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS: 5K01AR072131-02]
- New York State Stem Cell Science [NYSTEM: SDH C029550]
- Ines Mandl Research Foundation Fellowship
- Columbia University Herbert and Florence Irving Medical Center Dean's Precision Medicine Research Fellowship [UL1TR001873]
- Epicure Center at Columbia University Medical Center [5P30AR069632-02]
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.
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