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

被引:316
作者
Ebrahimian, T. G. [1 ]
Pouzoulet, F. [1 ]
Squiban, C. [1 ]
Buard, V. [1 ]
Andre, M. [2 ]
Cousin, B. [2 ]
Gourmelon, P.
Benderitter, M. [1 ]
Casteilla, L. [2 ]
Tamarat, R. [1 ]
机构
[1] IRSN, Serv Radiobiol Epidemiol, Direct Radioprotect Homme, Lab Radiopathol, F-92262 Fontenay Aux Roses, France
[2] CNRS, UMR 5241, UPS, IFR31, Toulouse, France
关键词
ADSCs; cell therapy; radiation; reepithelialization; angiogenesis; KERATINOCYTE GROWTH-FACTOR; RADIATION-THERAPY; EPIDERMAL-KERATINOCYTES; SKIN REGENERATION; IRRADIATED SKIN; STEM-CELLS; MODEL; RAT; DIFFERENTIATION; ANGIOGENESIS;
D O I
10.1161/ATVBAHA.108.178962
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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 day 14, 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. (Arterioscler Thromb Vasc Biol. 2009; 29: 503-510.)
引用
收藏
页码:503 / 510
页数:8
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