Application and progress of induced pluripotent stem cells in chronic wound healing: a narrative review

Chronic wounds provide a considerable therapeutic challenge owing to the inherent complexity of the healing process. Given the limitations of existing treatment options for chronic wounds, stem cell therapies have been explored as promising alternatives for promoting wound healing and tissue regeneration. However, traditional stem cell therapy is limited by invasive harvesting techniques, cellular heterogeneity, and limited cell survival in vivo. Induced pluripotent stem cells (iPSCs) have emerged as a novel and promising approach for treating chronic wounds. iPSCs can be derived from adult cells by in vitro induction of reprogramming factors, obviating the ethical dilemmas associated with embryonic stem cells. iPSCs can be generated from readily accessible adult somatic tissues such as skin or peripheral blood, providing, in principle, patient-matched cellular sources while avoiding embryo-derived material. These starting materials are typically obtained through minimally invasive sampling, such as a small skin punch biopsy or peripheral blood draw, and are generally less burdensome than bone marrow aspiration or surgical fat harvesting used for tissue-derived MSC procurement. Remarkably, iPSCs possess the unique capability to differentiate into all cell types in healthy skin, making them highly versatile for regenerative applications. iPSC-based cell therapies have demonstrated their potential to accelerate wound healing by enhancing angiogenesis, promoting tissue regeneration, improving cell migration, and modulating inflammation. Furthermore, iPSC-derived extracellular vesicles hold promise as a cell-free approach for wound repair. Moreover, iPSCs provide unrestricted access to various skin cells to generate complex three-dimensional tissue-engineered skin substitutes for grafting, disease modeling, and drug testing. Despite the significant advancements made in this field, safety, immunocompatibility, heterogeneity, and efficacy among iPSCs are still major hurdles. Overall, iPSC-derived cells, extracellular vesicles, and engineered skin constructs show promise in preclinical chronic wound models; however, clinical translation will require delivery strategies that maintain bioactivity within hostile wound microenvironments, standardized potency and dosing metrics, and rigorous long-term safety assessment under scalable Good Manufacturing Practice (GMP)-compatible workflows. This narrative review synthesizes current preclinical progress in iPSC-based approaches for chronic wounds and delineates the key mechanistic and translational priorities needed to advance toward regulatory approval and real-world implementation.