Adult stem cell therapy for skin wound healing: A translational perspective from bench to bedside

Complex wounds remain a substantial clinical burden, despite advances in surgical reconstruction and biomaterial-based therapies. Adult stem cell strategies for skin repair have attracted wide interest, but outcomes vary considerably and depend heavily on clinical context. Regenerative efficacy is shaped not only by the identity of the transplanted cells, but also by the functional state they acquire during ex vivo expansion and by the architectural complexity of the tissue to be restored. This review links two topics that are usually discussed separately: upstream advances in stem cell sourcing, culture systems, and manufacturing standardization, and downstream observations of how transplanted cells behave in vivo. We state how feeder dependence, chemically defined media, and three-dimensional culture platforms influence clonogenic hierarchy, inductive competence, paracrine activity, and lineage stability across adult stem cell populations relevant to skin repair, including epidermal stem cells (EpSCs), mesenchymal stem/stromal cells (MSCs), hair follicle stem cells (HFSCs), dermal papilla cells (DPCs), melanocytes (MCs), sebaceous gland stem cells (SeGSCs), and sweat gland stem cells (SGSCs). Across these systems, separating cells from their native niche during expansion or delivery tends to compromise long-term functional integration, whereas preserving or rebuilding epithelial-mesenchymal organization improves regenerative stability. Planar epithelial restoration with EpSC-based grafts has reached the highest clinical maturity, while regeneration of hair follicles, sebaceous glands, and sweat glands requires ordered three-dimensional assembly and remains limited by structural and manufacturing challenges. Melanocyte-based therapies sit apart from this hierarchy, restoring the epidermal melanin unit through coordinated integration with keratinocytes (KCs) rather than through three-dimensional organ reconstruction. By comparing these systems across levels of structural complexity and translational maturity, we outline how ex vivo cell states map onto in vivo regenerative outcomes, with implications for the design of scalable skin repair therapies.