R&D Scientist Academia Sinica, Taiwan (Republic of China)
Abstract: Peripheral artery disease (PAD) is a common vascular disorder caused by atherosclerosis and endothelial dysfunction, leading to reduced blood flow to the limbs and increasing the risk of critical limb ischemia, gangrene, or limb necrosis. Risk factors such as diabetes, hypertension, dyslipidemia, smoking, and obesity accelerate its progression. Despite its widespread prevalence, effective therapeutic options for PAD remain limited. To address this unmet need, we investigated the therapeutic potential of induced pluripotent stem cell (iPSC)-derived endothelial cells as a novel cell-based therapy for PAD.
Using a well-established hindlimb ischemia (HLI) model in immunodeficient NOD-SCID mice, we evaluated the therapeutic efficacy of iPSC-derived endothelial cells delivered via intramuscular injection at dosages ranging from 0.3 to 10 million cells, administered 24 hours post-HLI surgery. Blood flow recovery was assessed with laser Doppler imaging, and histological evidence was confirmed using immunofluorescence staining.
Following HLI surgery, blood flow in the ischemic limb decreased to less than 15%, indicating severe vascular compromise. At 28 days post-treatment, iPSC-derived endothelial cells demonstrated a dose-dependent effect, with the administration of 0.3–1×10⁶ cells significantly enhancing blood flow recovery. However, higher doses (10 million cells) were less effective compared to 1×10⁶ cells. Limb salvage scores showed a consistent trend with blood flow results. Histological analysis revealed that iPSC-derived endothelial cells contributed to neovascularization in the ischemic limbs.
This proof-of-concept study demonstrates the therapeutic potential of iPSC-derived endothelial cell therapy to restore vascular function in PAD. These findings offer a promising foundation for future translational and clinical applications, addressing a critical need in PAD treatment and improving the quality of life for affected individuals.
Funding Source: National Science and Technology Council (NSTC) Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
