Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation

Abstract

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