Human Adipose-Derived Stem Cells Enhance the Angiogenic Potential of Endothelial Progenitor Cells, But Not of Human Umbilical Vein Endothelial Cells

Abstract

One of the current challenges in the field of adipose tissue engineering is to promote sufficient vascularization to prevent cell death and to support adipose tissue formation. Thus, a novel strategy to enhance neovascularization of tissue-engineered adipose tissue might be the coimplantation of adipose-derived stem cells (ASCs) with endothelial progenitor cells (EPCs). However, no knowledge is given about the cellular interaction in vitro of human ASCs derived from subcutaneous fat tissue and EPCs derived from human peripheral blood. In this study, the first aim was to characterize ASCs and EPCs. Secondly, the two-dimensional Matrigel assay and the three-dimensional spheroid sprouting assay were applied for analyzing the ASC-EPC interaction in regard to formation of capillary-like structures by EPCs by ASC-conditioned medium (CM) or coculture of both cell types and compared to cocultures of ASCs and human umbilical vein endothelial cells (HUVECs). ASC-CM had no influence on the formation of capillary-like structures by EPCs. However, coculture with ASCs significantly enhanced the formation of capillary-like structures by EPCs; an effect that was not observed in cocultures of ASCs with HUVECs. Importantly, this increase in capillary-like structure formation by EPCs due to cell-cell contact was associated with significantly increased vascular endothelial growth factor (VEGF) secretion and VEGF-A mRNA expression, while inhibition of VEGF receptor tyrosine kinases completely abolished this effect. In conclusion, these data suggest that cellular communication occurs between ASCs and EPCs triggered by cell-cell contact or at least close proximity, which is partially mediated by secreted VEGF leading to the enhancement of angiogenic properties in EPCs, but not in HUVECs.