First, we studied the direct angiogenic differentiation potential of CardAP cells in a functional in vitro Matrigel tube formation assay. Since also paracrine-mediated mechanism of angiogenesis for cell therapy in cardiac regeneration are known, we further investigated the pro-angiogenic potential of CardAP cells on human umbilical vein endothelial cells (HUVECs) by using conditioned medium (CM) in the tube formation assay. Finally, we studied the secretion of the proangiogenic factors VEGF and IL-8 during the cultivation of CardAP cells.
The investigation of the angiogenic differentiation potential in tube formation assay revealed that CardAP cells showed endothelial structures but expression of endothelial markers could not be detected. Treating HUVECs with CM resulted in a significant up to a two-fold increase in total tube length and a up to a three fold increase in the number of branching points, indicating a pro-angiogenic effect of CardAP cells. Moreover, these cells secreted a mean of 576 ± 60 pg VEGF and a maximum mean of 99 ± 30 ng IL-8 per 105 cells.
Our findings revealed that CardAP cells mediate a pro-angiogenic effect in a paracrine manner, which might bean underlying mechanism of the cardio protective features of CardAP cells.