Effects of dermal multipotent cell transplantation on skin wound healing.

There is increasing evidence that dermis contains adult multipotent stem cells. To investigate the effects of dermis-derived multipotent cells on wound healing, we transplanted a clonal population of dermis-derived multipotent cells (termed as DMCs) by topical and systemic application into the skin wound of rats with simple wounds and rats with combined wound and radiation injury. Our results suggest that both topical and systemic transplantation of DMCs accelerate the healing process in rats with a simple wound; the promoting effect by topical transplantation occurs earlier than systemic transplantation. However, systemic transplantation of DMCs promotes the healing process in irradiated rats, while topical transplantation of DMCs fails. Further studies on the mechanisms of DMCs to promote wound healing indicate that the supernatant of DMCs could promote the proliferation of fibroblasts and epidermal cells; DMCs expressed transcripts of a series of cytokines and extracellular matrix molecules, including VEGF, PDGF, HGF, TGF-beta, ICAM-1, VCAM-1, and Fibronectin, which were closely related to the wound healing by DNA microarray analysis. The implanted DMCs can engraft into recipient skin wounded tissues after transplantation by the FISH analysis with Y-chromosome-specific probe. Systemic transplantation of DMCs also promotes the recovery of peripheral white blood cells in irradiated rats. These results demonstrate the different effects of DMCs on wound healing in non-irradiated and irradiated rats and illustrate the importance of optimizing wound healing via the topical or systemic transplantation of stem cells.