Abstract 1043: Resistance to Apoptosis and Proliferation of Adipose Progenitor Cells; Implications for Pro-Angiogenic Cell Therapy
Endothelial progenitor cells (EPC) emerge as therapeutic tools to promote ischemic tissue neovascularization. However, tissues hosting EPC with optimal therapeutic efficacy have not been identified. Stromal vascular fraction cells (SVF) from adipose tissue have been proposed as an efficient cell source for pro-angiogenic cell therapy. We compared the proliferation, apoptosis and efficacy in cell therapy of pro-angiogenic progenitor cells from various tissues, before and after culture in conditions favorable to EPC. SVF cells from human and mouse adipose tissue were highly resistant to apoptosis compared to mouse bone marrow-mononuclear cells (BMC) and human umbilical cord blood-EPC, as shown by FACS analysis and morphological evaluation of DAPI-stained nuclei. FACS analysis and direct cell counts revealed that SVF cells could readily be expanded. Culture for 7 d enhanced SVF survival (−92.9% apoptosis, +186.3% proliferation, p<0.05), whereas apoptosis increased in cultured BMC (+460.6%, p<0.05). In a mouse model of hindlimb ischemia, injection of cultured SVF cells promoted neovascularization significantly compared to cultured BMC (+38.7%, p<0.05). Conditioned media from SVF cells or adipocytes contained significant levels of adipose tissue-specific adiponectin and leptin. Conditioned media strongly increased BMC proliferation (+118.2%, p<0.05) and resistance to apoptosis (−83.2%, p<0.05), without affecting endothelial differentiation as shown by UEA-1 lectin binding and Dil-acetylated LDL incorporation. Moreover, culture in conditioned media stimulated the pro-angiogenic efficacy of BMC in ischemic hindlimbs (+46.8% versus control medium, p<0.05). Recombinant adiponectin recapitulated most these effects on BMC at near physiological doses, but not leptin. We thus identified resistance to apoptosis and proliferation as functional criteria to select adipose tissue SVF cells for pro-angiogenic therapy. Hence the intrinsic and secretory characteristics of SVF cells enhance their therapeutic potential. Moreover, our data suggest that adipose tissues can upregulate EPC survival and proliferation via adiponectin secretion. This may impact EPC biology in conditions associated with aberrant adiponectin levels or obesity.