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.
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.