# Effect of cell-based therapies on functional, hemodynamic, and histologic outcomes in a porcine model of peripheral arterial disease

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $603,929

## Abstract

Background & Significance. Peripheral artery disease (PAD) is a manifestation of atherosclerosis that
produces progressive narrowing and occlusion of the arteries supplying the legs. PAD usually presents as
claudication (leg pain and severe walking limitation), but some patients progress to limb threatening ischemia
and amputation. Standard therapies for claudication have limitations, so there remains a need to develop
treatments that improve limb function while decreasing the need for expensive care and procedures.
 Preliminary Work. We have developed and validated a porcine model of hindlimb ischemia (iliofemoral
artery excision) which recapitulates key aspects of the pathophysiology of human PAD/claudication, and used
it to test the efficacy of adipose-derived mesenchymal stem cells (ADMSCs). Our preliminary work shows that
injection of ADMSCs into the bed of the ligated/excised iliac artery produces (i) increased arteriogenesis, (ii)
enhanced muscle perfusion, and (iii) increased treadmill walking capacity in ADMSC-treated pigs compared to
untreated pigs.
 Hypothesis, Specific Aims. Our central hypothesis is that extra-arterial delivery of autologous ADMSCs
or derived exosomes will improve hemodynamic, histologic, and functional endpoints of the ischemic hindlimb
with associated arteriogenesis in a porcine model of PAD. We will explore our hypothesis using a porcine
model of hindlimb ischemia on a background of hypercholesterolemia and hypertension (induced with a high
fat/ high fructose/ high salt diet), which mimics PAD. The central hypothesis will be explored with three
Specific Aims:
 Aim 1. To determine whether extra-arterial administration of ADMSCs or ADMSC-derived exosomes will
stimulate arteriogenesis, improve hemodynamic/ perfusion endpoints, and modulate the local inflammatory
environment in a porcine model of PAD.
 Aim 2: To determine whether extra-arterial injection of ADMSCs or exosomes will improve ischemic
myopathy and treadmill performance in a porcine model of PAD.
 Aim 3: To determine whether combined application of ADMSCs and monocytes will induce arteriogenesis
in a perfused porcine artery system.
 Innovation. We will use a clinically-relevant large-animal model of PAD and novel techniques that were
developed by our research group to study the physiology and histopathology of the ischemic limb. We will also
utilize a derivative of porcine ADMSCs (i.e., the exosomes) which, if effective, offer numerous advantages over
conventional cellular therapy. In addition, we will characterize the effect of cell-based treatments on the local
inflammatory environment of the ischemic limb.

## Key facts

- **NIH application ID:** 10127549
- **Project number:** 5R01AG062198-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** MARK A CARLSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $603,929
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127549

## Citation

> US National Institutes of Health, RePORTER application 10127549, Effect of cell-based therapies on functional, hemodynamic, and histologic outcomes in a porcine model of peripheral arterial disease (5R01AG062198-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10127549. Licensed CC0.

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