An increase in peak excess pressure accounts for the rise in systolic blood pressure along the aorta

Endothelial cells derived from induced pluripotent stem cells (iPSC-ECs) have been shown to promote angiogenesis in vivo. Recently, an alternative method of generating endothelial cells has been developed, by directly differentiating fibroblasts into endothelial cells (iECs), bypassing the pluripotent intermediate. Here we compared survival, engraftment and pro-angiogenic potential of iECs versus iPSC-ECs in a mouse model of hindlimb ischaemia. Human iPSC-ECs and iECs were transduced with a firefly luciferase and green fluorescent protein reporter for bioluminescence imaging. They exhibited endothelial behavior in vitro, assessed by migration towards VEGF, uptake of acetylated-LDL and tubule formation on matrigel. NODSCID mice (n=7-9) underwent unilateral femoral artery ligation and received either control vehicle or 1x106 iPSCECs or iECs, via intramuscular injection. Recovery of the ischaemic limb was tracked for 14 days. Laser Doppler imaging after femoral artery ligation revealed enhanced blood perfusion recovery in the iEC group vs. control at day 7 (p<0.05), 10 and 14 (p<0.001). IPSC-ECs enhanced recovery vs. control at day 14 (p<0.05). At day 10, perfusion was significantly greater in iEC vs. iPSC-EC treated mice (p<0.01). IPSC-EC and iEC bioluminescent signals decreased over 14 days, but remained above background at all observed timepoints (p<0.0001). Analysis of skeletal muscle demonstrated significantly greater capillary density in the ischaemic limb of mice treated with iECs, vs. control (179±11 vs 125±10 capillaries/image; p<0.05). In conclusion, iECs have striking in vivo pro-angiogenic effects and appear to bemore potent than iPSC-ECs. These findings support further development of iECs for therapeutic angiogenesis.