In vitro angiogenesis properties of endothelial progenitor cells: a promising tool for vascularization of ex vivo engineered tissues.

Survival of ex vivo constructed tissues after transplantation is limited by insufficient oxygen and nutrient supply. Therefore, strategies aiming at the improvement of neovascularization of engineered tissues are a key issue. A method to enhance graft vascularization is to establish a primitive vascular plexus within the graft before transplantation by the use of cellular-based concepts. To explore the utility of endothelial progenitor cells (EPCs) for the ex vivo vascularization of tissue engineered grafts, we analyzed the in vitro angiogenic properties of this cell type in two different angiogenesis models: the 3-dimensional spheroid sprouting assay and the 2-dimensional matrigel assay. In both assays, EPCs were able to form tubelike structures, resembling early capillaries. This process was significantly enhanced by the addition of angiogenic growth factors. Direct comparison between EPCs and mature endothelial cells, represented by human umbilical vein endothelial cells (HUVECs), revealed that both cell types displayed an almost identical angiogenic potential. Other functional in vitro parameters such as angiogenic growth factor induced cell proliferation and cell survival were investigated as well, revealing a significantly decreased level of apoptosis of EPCs in relation to HUVECs under serum-deprived conditions. The observed survival advantage of EPCs along with the observation that EPCs perform very well in the above mentioned in vitro angiogenesis assays, make them an ideal autologous cell source for vascularization of ex vivo generated tissues. The attractiveness of this cell type for tissue engineering applications is strengthened further by the fact that these cells can be easily isolated from the peripheral blood of patients, thereby eliminating donor site morbidity.