Generating Skin‐Derived Precursor‐Like Cells From Human‐Induced Pluripotent Stem Cell‐Derived Skin Organoids

ABSTRACT Skin‐derived precursor (SKPs) cells are multipotent stem cells found in the dermis that contribute to wound healing and induce hair follicle neogenesis when transplanted. The clinical application of adult human SKPs, however, is hindered by their loss of potency after in vitro expansion. To overcome this challenge, we aimed to isolate SKPs from human‐induced pluripotent stem cell‐derived skin organoids (SKOs), to enable mass production of these cells for therapeutics. We developed a protocol to isolate skin‐derived precursor‐like cells (SKP‐like cells) from human SKOs. SKP‐like cells derived from SKOs exhibited characteristic spheroid morphology and were capable of self‐renewal in defined SKP growth medium. Immunofluorescence analysis confirmed the expression of key markers, including SOX2, fibronectin and S100β, within the SKP‐like cells. The findings of this pilot study shed light on the potential of SKO‐derived SKP‐like cells for future hair regenerative applications. Furthermore, this research highlights the application of human SKOs as a valuable source for isolating progenitor cells, aiming to advance hair regeneration and restore skin function.