# Modulating the Host Response to Tissue Engineered Vascular Grafts

> **NIH NIH F32** · OHIO STATE UNIVERSITY · 2021 · $32,190

## Abstract

PROJECT SUMMARY
Congenital heart disease (CHD) is a leading cause of death in newborns. Surgical intervention is the only
effective treatment, but is limited by morbidity from available prosthetic vascular grafts. Tissue engineering
offers a potential solution. We developed the first tissue engineered vascular graft (TEVG) for use in children.
FDA approval has now been obtained for investigation of this device. Although TEVG is safe and effective,
stenosis is the primary graft-related complication, representing a critical barrier for widespread clinical use.
Preliminary mechanisms indicate that host macrophage infiltration is essential for vascular neotissue formation,
however, excessive infiltration leads to stenosis. Macrophage infiltration is decreased by bone marrow-derived
mononuclear cells (BM-MNC) that are seeded onto the scaffold as part of the implantation protocol. BM-MNC
are transient and do not contribute to vascular tissue formation, but they do modulate the host inflammatory
response through an unknown paracrine mechanism. Preliminary data demonstrate that IL-10 levels correlate
positively with the number of BM-MNC and inversely with stenosis. Therefore, IL-10 represents a logical
cytokine for this paracrine mechanism. The goal of this project is to determine how IL-10 modulates the host-
TEVG interaction.
We will determine if IL-10 is necessary for BM-MNC to modulate host macrophage function using an IL-10 null
transgenic mouse BM-MNC donor compared to a wild-type BM-MNC donor. If BM-MNC IL-10 signaling is
required, then removing IL-10 in donor animals will eliminate the ability of BM-MNC to inhibit stenosis. Next, we
will determine if IL-10 is sufficient to modulate host macrophage function by administering systemic IL-10 and
assessing the degree of macrophage infiltration. We hypothesize that systemic administration of IL-10 will
decrease TEVG stenosis. We will identify the cellular source of IL-10 to determine if sorting BM-MNCs prior to
seeding decreases stenosis. Lastly, we will determine the role of recipient IL-10 signaling on neovessel
formation and stenosis.
Successful completion of these aims will result in an improved mechanistic understanding of vascular
neotissue formation, stenosis and how the host interacts with biomaterials. This approach will allow us to move
away from empiric design and towards rational design of TEVG. This will contribute to the successful
translation of TEVG into widespread clinical use and the improvement of outcomes for children with congenital
cardiac anomalies.

## Key facts

- **NIH application ID:** 10128195
- **Project number:** 5F32HL144120-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jenny Cathryn Barker
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $32,190
- **Award type:** 5
- **Project period:** 2020-02-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128195

## Citation

> US National Institutes of Health, RePORTER application 10128195, Modulating the Host Response to Tissue Engineered Vascular Grafts (5F32HL144120-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10128195. Licensed CC0.

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