Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing

T.G. Ebrahimian (1) , F. Pouzoulet (1) , C. Squiban (1) , V. Buard (1) , M. André (2) , B. Cousin (2) , P. Gourmelon (1) , M. Benderitter (1) , L. Casteilla (2) , R. Tamarat (1)

1 IRSN/DRPH/SRBE - Service de RadioBiologie et d'Epidémiologie
2 LMPM - Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31]

OBJECTIVE: We hypothesized that adipose tissue may contain progenitors cells with cutaneous and angiogenic potential. METHODS AND RESULTS: Adipose tissue-derived stroma cells (ADSCs) were administrated to skin punched wounds of both nonirradiated and irradiated mice (20 Gy, locally). At day14, ADSCs promoted dermal wound healing and enhanced wound closure, viscolesticity, and collagen tissue secretion in both irradiated and nonirradiated mice. Interestingly, GFP-positive ADSCs incorporated in dermal and epidermal tissue in vivo and expressed epidermal markers K5 and K14. Cultured ADSCs in keratinocyte medium have been shown to differentiate into K5- and K14-positive cells and produced high levels of KGF. At Day 7, ADSCs also improved skin blood perfusion assessed by laser Doppler imaging, capillary density, and VEGF plasma levels in both irradiated and nonirradiated animals. GFP-positive ADSCs incorporated into capillary structures in vivo and expressed the endothelial cell marker CD31. Finally, in situ interphase fluorescence hybridization showed that a small number of ADSCs have the potential to fuse with endogenous keratinocytes. CONCLUSION: ADSCs participate in dermal wound healing in physiological and pathological conditions by their ability to promote reepithelialization and angiogenesis. Hence, adipose lineage cells represent a new cell source for therapeutic dermal wound healing. © 2009 American Heart Association, Inc.

Mots clés: alpha actin; CD31 antigen; collagen; cytokeratin 14; cytokeratin 5; green fluorescent protein; keratinocyte growth factor; vasculotropin; vasculotropin A; adipose tissue; adipose tissue derived stromal cell; angiogenesis; animal experiment; animal model; animal tissue; article; capillary density; cell therapy; controlled study; dermis; endothelium cell; epidermis; epithelization; fluorescence in situ hybridization; interphase; keratinocyte; laser Doppler flowmetry; male; mouse; nonhuman; perfusion; priority journal; protein blood level; secretion; skin injury; stroma cell; viscoelasticity; wound closure; wound healing; animal; blood; blood flow; C57BL mouse; capillary; cell culture; cell differentiation; cell fusion; cell lineage; cell transplantation; cytology; genetics; metabolism; pathophysiology; radiation exposure; reporter gene; skin; time; transplantation; vascularization; Adipose Tissue; Animals; Capillaries; Cell Differentiation; Cell Fusion; Cell Lineage; Cell Transplantation; Cells; Cultured; Endothelial Cells; Fibroblast Growth Factor 7; Genes; Reporter; Green Fluorescent Proteins; Keratinocytes; Male; Mice; Inbred C57BL; Models; Animal; Neovascularization; Physiologic; Regional Blood Flow; Skin; Stromal Cells; Time Factors; Vascular Endothelial Growth Factor A; Wound Healing

Domaines: Sciences du Vivant [q-bio]

T.G. Ebrahimian, F. Pouzoulet, C. Squiban, V. Buard, M. André, et al.. Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing. Arteriosclerosis, Thrombosis, and Vascular Biology, 2009, 29 (4), pp.503-510. ⟨10.1161/ATVBAHA.108.178962⟩. ⟨hal-02985051⟩