Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation

Li-Ping Liu; Yu-Mei Li; Ning-Ning Guo; Shu Li; Xiaolong Ma; Yi-Xuan Zhang; Yimeng Gao; Jian-Ling Huang; Dong-Xu Zheng; Lu-Yuan Wang; Hui Xu; Lijian Hui; Yun-Wen Zheng

doi:10.1016/j.celrep.2019.03.046

Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation

Cell Rep. 2019 Apr 9;27(2):455-466.e5. doi: 10.1016/j.celrep.2019.03.046.

Authors

Li-Ping Liu¹, Yu-Mei Li², Ning-Ning Guo³, Shu Li³, Xiaolong Ma⁴, Yi-Xuan Zhang³, Yimeng Gao⁴, Jian-Ling Huang³, Dong-Xu Zheng⁵, Lu-Yuan Wang³, Hui Xu³, Lijian Hui⁶, Yun-Wen Zheng⁷

Affiliations

¹ Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu 212001, China; Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu 212001, China; Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
² Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu 212001, China; Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu 212001, China. Electronic address: l.yumei@aliyun.com.
³ Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu 212001, China; Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu 212001, China.
⁴ State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Science, Shanghai 200031, China.
⁵ Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
⁶ State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Science, Shanghai 200031, China; School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China; Stem Cell and Regenerative Medicine Innovation Academy, Beijing 100101, China. Electronic address: ljhui@sibcb.ac.cn.
⁷ Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu 212001, China; Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan; School of Medicine, Yokohama City University, Yokohama 236-0004, Japan. Electronic address: ywzheng@md.tsukuba.ac.jp.

PMID: 30970249
DOI: 10.1016/j.celrep.2019.03.046

Abstract

Induced pluripotent stem cells (iPSCs) are a promising melanocyte source as they propagate indefinitely and can be established from patients. However, the in vivo functions of human iPSC-derived melanocytes (hiMels) remain unknown. Here, we generated hiMels from vitiligo patients using a three-dimensional system with enhanced differentiation efficiency, which showed characteristics of human epidermal melanocytes with high sequence similarity and involved in multiple vitiligo-associated signaling pathways. A modified hair follicle reconstitution assay in vivo showed that MITF⁺PAX3⁺TYRP1⁺ hiMels were localized in the mouse hair bulb and epidermis and produced melanin up to 7 weeks after transplantation, whereas MITF⁺PAX3⁺TYRP1^- hiMelanocyte stem cells integrated into the bulge-subbulge regions. Overall, these data demonstrate the long-term functions of hiMels in vivo to reconstitute pigmented hair follicles and to integrate into normal regions for both mature melanocytes and melanocyte stem cells, providing an alternative source of personalized cellular therapy for depigmentation.

Keywords: 3D differentiation system; EB; cellular transplantation therapy; embryoid body; hair follicle reconstitution in vivo; hair follicle stem cells; hiMels; human epidermal melanocytes; human iPSC-derived melanocytes; iPSCs; melanocyte stem cells; patient induced pluripotent stem cells; three-dimensional differentiation system; vitiligo.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Induced Pluripotent Stem Cells / metabolism*
Induced Pluripotent Stem Cells / transplantation*
Melanocytes / metabolism*
Mice
Rabbits
Stem Cell Transplantation / methods*
Transplantation, Autologous