Engineered Skin Substitute Regenerates the Skin with Hair Follicle Formation

Jinmei Wang; Xiaoxiao Wang; Jundong Xie; Bin Yao; Miaohua Mo; Danjun Ma; Chen Huang; Renhe Xu; Xiaobing Fu; Edward E Tredget; Yaojiong Wu

doi:10.3390/biomedicines9040400

Engineered Skin Substitute Regenerates the Skin with Hair Follicle Formation

Biomedicines. 2021 Apr 8;9(4):400. doi: 10.3390/biomedicines9040400.

Authors

Jinmei Wang^{1

2

3}, Xiaoxiao Wang^{2

4

5}, Jundong Xie^{2

3

4}, Bin Yao^{2

3

4}, Miaohua Mo^{2

3

4}, Danjun Ma¹, Chen Huang⁶, Renhe Xu⁷, Xiaobing Fu^{8

9}, Edward E Tredget¹⁰, Yaojiong Wu^{2

3

4}

Affiliations

¹ School of Mechanical Engineering, Dongguan University of Technology, 1 Daxue Rd, Dongguan 523830, China.
² iBHE, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
³ State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
⁴ Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen 518055, China.
⁵ Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China.
⁶ Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
⁷ Faculty of Health Sciences, University of Macau, Macau 999078, China.
⁸ Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing 100088, China.
⁹ Stem Cell and Tissue Regeneration Laboratory, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing 100084, China.
¹⁰ Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, AB T6G2B7, Canada.

Abstract

Currently, engineered skin substitutes (ESS) are unable to regenerate cutaneous appendages. Recent studies have shown that skin-derived precursors (SKPs), which are extensively available, have the potential to induce hair follicle neogenesis. Here, we demonstrate that ESS consisting of culture-expanded SKPs and epidermal stem cells (Epi-SCs) reconstitute the skin with hair follicle regeneration after grafting into nude mice. SKPs seeded in a C-GAG matrix proliferated and expressed higher levels of hair induction signature genes-such as Akp2, Sox2, CD133 and Bmp6-compared to dermal fibroblasts. Moreover, when ESS prepared by seeding a mixture of culture-expanded murine SKPs and human adult Epi-SCs into a C-GAG matrix was grafted into full-thickness skin wounds in nude mice, black hairs were generated within 3 weeks. Immunofluorescence analysis showed that the SKPs were localized to the dermal papillae of the newly-formed hair follicle. Our results indicate that SKPs can serve as the hair-inductive cells in ESS to furnish it with hair genesis potential.

Keywords: engineered skin substitute; hair follicle neogenesis; skin derived precursors.

Abstract

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