Tissue engineering of human hair follicles using a biomimetic developmental approach

Hasan Erbil Abaci; Abigail Coffman; Yanne Doucet; James Chen; Joanna Jacków; Etienne Wang; Zongyou Guo; Jung U. Shin; Colin A. Jahoda; Angela M. Christiano

doi:10.1038/s41467-018-07579-y

Tissue engineering of human hair follicles using a biomimetic developmental approach

Hasan Erbil Abaci, Abigail Coffman, Yanne Doucet, James Chen, Joanna Jacków, Etienne Wang, Zongyou Guo, Jung U. Shin, Colin A. Jahoda, Angela M. Christiano^*

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

210 Citations (Scopus)

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Abstract

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.

Original language	English
Article number	5301
Number of pages	11
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	13 Dec 2018
DOIs	https://doi.org/10.1038/s41467-018-07579-y
Publication status	Published - 13 Dec 2018

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Tissue engineering of human hair follicles using_JACKOW_Publishedonline14December2018_GOLD VoR (CC BY)Final published version, 15.1 MBLicence: CC BY

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title = "Tissue engineering of human hair follicles using a biomimetic developmental approach",

abstract = "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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AU - Abaci, Hasan Erbil

AU - Coffman, Abigail

AU - Doucet, Yanne

AU - Chen, James

AU - Jacków, Joanna

AU - Wang, Etienne

AU - Guo, Zongyou

AU - Shin, Jung U.

AU - Jahoda, Colin A.

AU - Christiano, Angela M.

PY - 2018/12/13

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N2 - 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.

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.

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Tissue engineering of human hair follicles using a biomimetic developmental approach

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