# Applying induced pluripotent stem cell derived endothelial cells to regenerative therapy in chronic limb threatening ischemia

> **NIH VA I21** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

Peripheral arterial disease (PAD) is highly prevalent among the Veteran population. Veterans
experience PAD onset at an earlier age than their non-Veteran counterparts and are at increased risk
of experiencing adverse outcomes from peripheral arterial disease. Chronic limb threatening ischemia
(CLTI), the most severe form of peripheral arterial disease, is a significant cause of morbidity, including
persistent pain at rest, neuronal dysfunction, and ultimately limb loss. While endovascular and surgical
treatment options have advanced, many patients are not candidates for revascularization due to
anatomic constraints or co-morbidities. Therapies for these “no-option CLTI” patients are limited to
palliation consisting of pain control and major amputation, both of which lead to significant morbidity
and disability. Improved therapeutic modalities to treat this “no-option CLTI” population and to
prevent limb loss are desperately needed.
 Stem cell-based therapies have emerged as a promising new modality to treat this “no-option CLTI”
population. The advent of induced pluripotent stem cell (iPSC) technology allows for an infinitely
reproducible and scalable source of stem cells. This technology was rendered applicable to vascular
disease by the establishment of reliable directed differentiation of said stem cells to the myriad vascular
cell types required for a functional blood vessel. Our prior work overcame the barrier of premature loss
of EC function and replicative senescence in culture, opening the door to the next steps in developing
iPSC-EC therapeutics.
 This proposal aims to (1) validate the survival and function of clinical grade iPSC-ECs in implantable
and resorbable platelet lysate hydrogels, and (2) quantify the restoration of limb perfusion and function
after implantation of hydrogels containing iPSC-ECs into ischemic mouse hindlimbs. This work will
generate a critical pre-clinical animal model of utilizing PAD patient-derived iPSC-ECs to promote local
vascular regeneration in ischemic limbs as a novel therapy for CLTI.

## Key facts

- **NIH application ID:** 10890651
- **Project number:** 5I21RX004399-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Katherine Elizabeth Hekman
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-04-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890651

## Citation

> US National Institutes of Health, RePORTER application 10890651, Applying induced pluripotent stem cell derived endothelial cells to regenerative therapy in chronic limb threatening ischemia (5I21RX004399-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10890651. Licensed CC0.

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