Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation

Summary: 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 th...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2019-04-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719303626
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author 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
author_facet 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
author_sort Li-Ping Liu
collection DOAJ
description Summary: 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. : Liu et al. show that patient iPSC-derived melanocytes maintain long-term functionality in mice by integrating into regions normally containing mature melanocytes and melanocyte stem cells and reconstituting pigmented hair follicles. These insights provide an alternative source for personalized cellular therapy for depigmentation. Keywords: patient induced pluripotent stem cells, iPSCs, human iPSC-derived melanocytes, hiMels, hair follicle reconstitution in vivo, embryoid body, EB, three-dimensional differentiation system, 3D differentiation system, cellular transplantation therapy, vitiligo, melanocyte stem cells, hair follicle stem cells, human epidermal melanocytes
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spelling doaj.art-84ab925cef5b4788b98d1ea47eec24082022-12-21T22:54:57ZengElsevierCell Reports2211-12472019-04-01272455466.e5Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous TransplantationLi-Ping Liu0Yu-Mei Li1Ning-Ning Guo2Shu Li3Xiaolong Ma4Yi-Xuan Zhang5Yimeng Gao6Jian-Ling Huang7Dong-Xu Zheng8Lu-Yuan Wang9Hui Xu10Lijian Hui11Yun-Wen Zheng12Institute 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, JapanInstitute 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; Corresponding authorInstitute 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, ChinaInstitute 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, ChinaState 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, ChinaInstitute 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, ChinaState 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, ChinaInstitute 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, ChinaFaculty of Medicine, University of Tsukuba, Ibaraki 305-8575, JapanInstitute 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, ChinaInstitute 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, ChinaState 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; Corresponding authorInstitute 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; Corresponding authorSummary: 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. : Liu et al. show that patient iPSC-derived melanocytes maintain long-term functionality in mice by integrating into regions normally containing mature melanocytes and melanocyte stem cells and reconstituting pigmented hair follicles. These insights provide an alternative source for personalized cellular therapy for depigmentation. Keywords: patient induced pluripotent stem cells, iPSCs, human iPSC-derived melanocytes, hiMels, hair follicle reconstitution in vivo, embryoid body, EB, three-dimensional differentiation system, 3D differentiation system, cellular transplantation therapy, vitiligo, melanocyte stem cells, hair follicle stem cells, human epidermal melanocyteshttp://www.sciencedirect.com/science/article/pii/S2211124719303626
spellingShingle 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
Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation
Cell Reports
title Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation
title_full Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation
title_fullStr Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation
title_full_unstemmed Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation
title_short Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation
title_sort therapeutic potential of patient ipsc derived imelanocytes in autologous transplantation
url http://www.sciencedirect.com/science/article/pii/S2211124719303626
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