Background— Adipose tissue development and remodeling are closely associated with the growth of vascular network. We hypothesized that adipose tissue may contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. Methods and Results— In mice, cultured stromal-vascular fraction (SVF) cells from adipose tissue have a great proangiogenic potential, comparable to that of bone marrow mononuclear cells in the mouse ischemic hindlimb model. Similarly, cultured human SVF cells differentiate into endothelial cells, incorporate into vessels, and promote both postischemic neovascularization in nude mice and vessel-like structure formation in Matrigel plug. In vitro, these cells represent a homogeneous population of CD34- and CD13-positive cells, which can spontaneously express the endothelial cell markers CD31 and von Willebrand factor when cultured in semisolid medium. Interestingly, dedifferentiated mature human adipocytes have the potential to rapidly acquire the endothelial phenotype in vitro and to promote neovascularization in ischemic tissue and vessel-like structure formation in Matrigel plug, suggesting that cells of endothelial and adipocyte phenotypes may have a common precursor. Conclusions— This study demonstrates, for the first time, that adipocytes and endothelial cells have a common progenitor. Such adipose lineage cells participate in vascular-like structure formation in Matrigel plug and enhance the neovascularization reaction in ischemic tissue. These results also highlight the concept that adipose lineage cells represent a suitable new cell source for therapeutic angiogenesis in ischemic disease.

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Abstract-Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. Key Words: cardiomyocytes Ⅲ adipose tissue Ⅲ differentiation Ⅲ stem cells Ⅲ cell therapy C ardiomyocyte differentiation mainly takes place during neonatal and perinatal life. In adult life, the regenerative potential of cardiac tissue is limited and is not sufficient to prevent from the degeneration occurring in pathological conditions such as myocardial infarction. 1 Cell transplantation seems to be an alternative to overcome this problem. 2 This led to numerous investigations to identify a putative source of transplanted cells and to better understand cardiomyocyte proliferation and differentiation in order to drive the fate of stem cells toward this process. Different sources, ie, embryonic, fetal, and adult cells have been investigated and tested. 3-8 Among them, mesenchymal stem cells (MSCs) isolated from bone marrow are accepted to give rise to connective tissue cell types. Their differentiation toward cardiomyocyte was obtained in vitro and in vivo. However, immortalized MSCs and treatment with the DNA demethylation agent 5-azacytidine was necessary to reveal their cardiogenic potential in vitro. 6 Adipose tissues are mesodermic tissues, which develop during perinatal and postnatal life. 9 They are strongly involved in various metabolic disorders such as obesity. Tremendous changes in adipose mass are achieved through highly controlled processes such as angiogenesis, precursor recruitment, proliferation, differentiation, dedifferentiation, and apoptosis as well. More recently, differentiation of cells derived or purified from adipose tissue toward phenotypes different from adipocyte was described. 10 -13 However, the characterization of cells with such potential remains to be done. The present statement is that adipose tissue consists of mature adipocytes and the stroma vascular fraction (SVF). SVF is a heterogeneous cell population. Among them the identified ones are vascular cells (endothelial, smooth muscle cell, circulating blood cells) and an undefined fibroblast-like cell population recently described as a multipotential stem cell population for various mesodermic lineage. 10 -13 This led us to test the in vitro cardiomyogenic potential of cells purified from adipose tissue. In the results reported in this study, adipose-derived cells (SVF cells) from primary culture spontaneously differentiate into cells with morphological, molecular, and functional properties of cardiomyocytes. Materials and Methods AnimalsSix-week-old adult male C57Bl/6N mice (Harlan, France) were housed in conventional animal quarters (SPS barrier facility). Mice were killed by cervical dislocation under CO 2 anesthesia. All procedures were performed according to SELASA norms.