Autologous fat tissue has been used as a potential filler for soft-tissue defects, despite unpredictable clinical outcomes and low graft survival. Co-transplantation of adipose-derived stem cells (ASCs) is an alternative therapeutic approach to effectively enhance the survival and quality of transplanted fat tissue by increasing neovascularization. Nevertheless, the mechanisms by which ASCs exerted their angiogenic effects remain obscure. ASCs can secrete several angiogenic growth factors, for example vascular endothelial growth factor, hepatocyte growth factor and basic fibroblast growth factor. Hypoxic conditions may promote the proliferation of ASCs and their secretion. However, the differentiation of ASCs into endothelial cells (ECs), pericytes and smooth muscular cells in vivo has not been confirmed. The role of ASCs early after aspirated fat transplantation may be to induce new vessels from the recipient region to grow around and into the graft by releasing significant amounts of angiogenic growth factors rather than to differentiate into ECs, pericytes or smooth muscular cells forming new vessels, an effect that might be enhanced by hypoxia.