Abstract 616: Cell Therapy Based On Adipose Tissue-derived Stroma Cells Promotes Physiological And Pathological Wound Healing.
Background: We hypothesized that adipose tissue may contain progenitors cells with cutaneous and angiogenic potential and that therapy based on adipose tissue-derived progenitors cells administration may constitute a promising cell therapy in patients with impaired dermal wound healing.
Methods and results: Adipose tissue-derived stroma cells (ADSC) were administrated to skin punched wounds of both non-irradiated and irradiated mice (20 Gy, locally). ADSC promoted dermal wound healing and enhanced wound closure, viscolesticity and collagen tissue secretion by 2.8-, 2.1- and 2.5-fold respectively in non irradiated mice and by 2.6-, 1.4- and 2.2-fold, respectively in irradiated mice when compared to PBS injected animals (p<0.05). Interestingly, GFP-positive ADSC incorporated in dermal and epidermal tissue in vivo and expressed epidermal markers K5 and K14. Cultured ADSC in keratinocyte medium have been shown to differentiate into K5- and K14-positive cells and produced high levels of KGF. ADSC also improved skin blood perfusion assessed by laser Doppler Imaging, capillary density and VEGF plasma levels by 2.2-, 3.2- and 5-fold respectively in non irradiated mice and by 1.9-, 1.9- and 3.5-fold, respectively in irradiated mice when compared to PBS injected animals (p<0.01). GFP-positive ADSC incorporated into capillary structures in vivo and expressed endothelial cell marker CD31. Finally, in situ interphase fluorescence hybridization was used to detect cell fusion. GFP-ADSC isolated from female mice were transplanted to male mice. We observed GFP-positive cells stained with 2 X chromosome probe and 1 Y chromosome probe suggesting that ADSC can fuse spontaneously in our experimental conditions.
Conclusion: This study demonstrates, for the first time that ADSC participate to dermal wound healing in physiological and pathological conditions by both cell fusion, differentiation in keratinocyte cells and KGF secretion. ADSC also trigger angiogenesis. Hence, adipose lineage cells represent a new cell source for therapeutic dermal wound healing.