Skin-derived precursor cells promote wound healing in diabetic mice.

BACKGROUND Impaired wound healing as one of the complications arising from diabetes mellitus is a serious clinical issue. Recently, various cell therapies have been reported for promotion of wound healing. Skin-derived precursor cells (SKPs) are multipotent adult stem cells with the tendency to differentiate into neurons. We investigated the potency of promoting diabetic wound healing by the application of SKPs. METHODS Skin-derived precursor cells isolated from diabetic murine skin were cultured in sphere formation medium. At passage 2, they were suspended in phosphate-buffered saline (PBS), and applied topically to full-thickness excisional cutaneous wounds in diabetic mice. Application of PBS served as controls (n = 21 for each group; n = 42 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 10 and 28 days and then processed, sectioned, and stained (CD31, α-smooth muscle actin, and neurofilament heavy chain) to quantify vascularity and neurofilaments. RESULTS Wounds treated with SKPs demonstrated a significantly decreased time to closure (18.63 days) compared with PBS-control wounds (21.72 days, P < 0.01), and a significant improvement in percentage closure at 7, 10, 14, and 18 days compared with PBS-control wounds (P < 0.01). Histological analysis showed that the Capillary Score (the number of vessels/mm2) was significantly higher in SKP-treated wounds at day 10 but not at day 28. Nerve Density (the number of neurofilaments/mm2) had increased significantly in SKP-treated wounds at day 28 compared with control group. Some applied SKPs were stained by neurofilament heavy chain, which demonstrates that SKPs directly differentiated into neurons. CONCLUSIONS Skin-derived precursor cells promoted diabetic wound healings through vasculogenesis at the early stage of wound healing. Skin-derived precursor cells are a possible therapeutic tool for diabetic impaired wound healing.