# Elucidating the Endothelial-Smooth Muscle Cell Interactions in Marfan Syndrome Using iPSCs

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2024 · $22,371

## Abstract

Project Summary
Marfan Syndrome (MFS) is a genetic disorder of the connective tissue caused by mutations in the fibrillin-
1(FBN1) gene. These mutations cause increased vascular smooth muscle cell (vSMC) apoptosis, increased
matrix metalloproteinase (MMP) expression, excessive elastin degeneration and collagen overexpression;
weakening the vascular architecture, impair hemodynamic regulation, and ultimately leading to severe vascular
complications. Primary cells, tissue explants, and transgenic mouse models suffer from insufficiencies that
inhibit development of novel insights into disease pathogenesis or potential therapeutics; warranting new
modeling platforms. Recent advances in biomaterials have generated vascular grafts that mimic properties of
the extracellular matrix (ECM) in the natural vasculature. Human induced pluripotent stem cells (hiPSC) are an
ideal, patient specific renewable cell source that provides an avenue to study how genetic diseases effect cell
mechanobiology, signaling and function to better development therapeutics. Here, using a natural fibrin-based
vascular graft and hiPSCs from patients with Marfan Syndrome, we aim to: (1) fully characterized both ECs
and contractile vSMCs from hiPSCs derived from Marfan patients, (2) study the responses of hiPSC-ECs to
shear force and hiPSC-vSMCs to circumferential strain, (3) study the impacts of mechanical forces (i.e. shear
force and circumferential strain) and paracrine signaling in a co-culture model, specifically reactive oxygen
species(ROS), on vSMC phenotype and rate of graft degradation using the fibrin-based vascular graft. Our
multidisciplinary approach underpinning this project will elucidate key mediators of MFS disease progression
towards early detection and therapeutic targets.

## Key facts

- **NIH application ID:** 10757463
- **Project number:** 5F31HL156741-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Franklyn Hall
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $22,371
- **Award type:** 5
- **Project period:** 2021-12-31 → 2024-06-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757463

## Citation

> US National Institutes of Health, RePORTER application 10757463, Elucidating the Endothelial-Smooth Muscle Cell Interactions in Marfan Syndrome Using iPSCs (5F31HL156741-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10757463. Licensed CC0.

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