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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:503.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Cell Therapy Based on Adipose Tissue-Derived Stromal Cells Promotes Physiological and Pathological Wound Healing

T.G. Ebrahimian; F. Pouzoulet; C. Squiban; V. Buard; M. André; B. Cousin; P. Gourmelon; M. Benderitter; L. Casteilla; R. Tamarat

From the Institut de Radioprotection et de Surete Nucleaire IRSN, Service de Radiobiologie d'Epidemiologie (T.G.E, F.P., C.S., V.B., M.B., R.T.), Direction de la Radioprotection de l'Homme, Laboratoire de RadioPathologie, Fontenay-aux-Roses Cedex, France; and UMR 5241 CNRS UPS, IFR31 (M.A., B.C., L.C.), Toulouse, France.

Correspondence to Radia Tamarat, IRSN, B.P. no. 17, F-92262 Fontenay-aux-Roses Cedex, France. E-mail radia.tamarat{at}irsn.fr

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.

Adipose tissue-derived stroma cell (ADSC) administration promoted wound healing. Interestingly, GFP-positive ADSCs incorporated in dermal and epidermal tissue in vivo and expressed epidermal markers K5 and K14. ADSCs also improved skin blood perfusion and capillary density, at least through their ability to incorporate into capillary structures in vivo.

Key Words: ADSCs • cell therapy • radiation • reepithelialization • angiogenesis