Efficient generation of endothelial cells from induced pluripotent stem cells derived from a patient with peripheral arterial disease

Abstract

Peripheral arterial disease (PAD) is caused by atherosclerotic plaque accumulation, which results in ischemia in lower extremity ischemia. Cell-based therapy using endothelial progenitor cells (EPCs) or endothelial cells (ECs) has been challenging due to an insufficient number and replicative senescence of primary cells isolated from patients. To overcome this limitation, we generated induced pluripotent stem cells (iPSCs) from a patient with PAD for the first time. The patient-specific iPSCs have unlimited proliferation and can be used to generate a clinically relevant number of functional ECs. Here we developed a strategy to efficiently generate high EC yields within 5 days of differentiation. The generated iPSC-derived ECs from a PAD patient were phenotypically and functionally similar to the primary blood outgrowth endothelial cells (BOECs) and iPSC-ECs derived from healthy donors as evidenced by expression of EC-specific markers, capillary-like tube-forming potential, and the ability to uptake acetylated low-density lipoprotein (Ac-LDL). Our approach may provide an alternative renewable source of large-scale ECs for regenerative therapy. This study represents the first step toward the development of an autologous cell-based strategy for the treatment of PAD in the future.