Upregulation of Bcl-2 enhances secretion of growth factors by adipose-derived stem cells deprived of oxygen and glucose

Abstract

There is an increasing recognition that beneficial effects of adipose-derived stem cell (ADSC) therapy may depend largely on the secretion of multiple growth factors. This study modified ADSCs with the Bcl-2 gene in order to increase the secretion of growth factors during oxygen-glucose deprivation (OGD). The phenotypes of human ADSCs that were passaged 4 times were analyzed using flow cytometry. Then, ADSCs were genetically modified with Bcl-2 and Bcl-2 gene transduction was verified with Western blotting. Proliferative capacity and multipotent differentiation properties were evaluated in Bcl-2-modified ADSCs. Secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF) was evaluated using an enzyme-linked immunosorbent assay (ELISA) during OGD. Human ADSCs that were passaged 4 times expressed stem cell-associated markers but not a fibroblast marker or a hematopoietic stem cell marker. The Bcl-2 gene was efficiently transfected into ADSCs; Bcl-2 modification did not affect the proliferative and multilineage differentiation capacity of ADSCs. In addition, Bcl-2 overexpression enhanced the secretion of VEGF, bFGF, and HGF by 14.47%, 16.9%, and 91%, respectively, compared to ADSCs alone that were deprived of oxygen and glucose. These data suggest that Bcl-2 overexpression enhances secretion of angiogenic growth factors by ADSCs deprived of oxygen and glucose.