iMSCs vs MSCs: Comparative Features and Therapeutic Potential in Wound Healing

Regenerative medicine is evolving exponentially due to the wide range of therapeutic applications of mesenchymal stromal cells (MSCs), including wound healing. Although the translation of tissue-derived primary MSCs (tMSCs) into clinical practice remains scarce despite preclinical success. The primary causes are donor-associated and batch-to-batch variations, replicative senescence, and the inability of large-scale manufacturing. Recent studies show that the induced MSCs (iMSCs) derived from reprogrammed induced pluripotent stem cells (iPSCs) offer distinct advantages over conventional tMSCs. This review aims to provide a comprehensive comparative analysis of the cellular characteristics, secretome composition (including growth factors, cytokines, and exosome cargo), regenerative capacities, and therapeutic potentials of tMSCs and iMSCs, with a specific focus on their applications in wound healing and tissue regeneration. The iMSCs surpass tMSCs by providing superior regenerative, immunomodulatory, and angiogenic benefits, along with unmatched consistency and scalability. iMSCs and their derivatives have exhibited remarkable capacities to promote angiogenesis, ECM production, re-epithelialization, tissue regeneration, and scarless wound healing in diabetic, cutaneous, mucosal, and burn wounds. These advantages position iMSCs as a next-generation cell therapy for managing both acute and chronic wounds, promising improved clinical outcomes and broader applicability.