# Mechanical Conditioning of Mesenchymal Stem Cells for Enhanced Recellularized Vascular Grafts

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $391,250

## Abstract

Cardiovascular diseases are the most common cause of death worldwide and exert a massive social and
financial burden on the healthcare system of the United States. The formation of occlusive vascular disease in
the coronary and peripheral vascular often necessitates bypass graft surgery to provide a conduit for flow
around the blockages. While this surgery can provide restoration of flow for the patient, there is only a limited
amount of autologous arteries or veins in the patients that can be harvested for use in these surgeries. Often
these vessels also have the presence of vascular disease and in many cases fail relatively rapidly due to
accelerated occlusion by restenosis. Small diameter synthetic vascular grafts have proven extremely
challenging to develop due to thrombosis and graft failure. A promising approach to this problem is to use
tissue engineered vascular grafts to create new conduits to be used in bypass surgeries. Decellularized
arteries are a very appealing approach for creating tissue engineered scaffolds that have mechanical
properties similar to native vessels, are not immunogenic and can be seeded with cells harvested from the
patient. Mechanical forces are an essential part of vascular homeostasis and provide needed stimuli to
maintain blood vessel function. In addition, the mechanical microenvironment is key in regulating the
remodeling of the vascular system during embryological development and during injury. Here, we will use
mechanical forces in combination with biochemical signals and pharmacological inhibitors to optimize the
generation of vascular smooth muscle cells (vSMCs) and endothelial cells from bone marrow mesenchymal
stem cells (MSCs). Bone marrow MSCs are easily obtainable from patients and consequently are very
appealing for providing autologous source of cells. These mechanically conditioned MSCs will be seeded into
tissue engineered grafts created by decellularizing arteries. Our major goals are to identify optimal conditions
to differentiate MSCs into vSMC and endothelial cell phenotype, and test whether mechanically conditioned
MSCs are superior to non-conditioned MSCs when used in recellularized vascular grafts. We will approach this
objective through the following specific aims: (1) Use high throughput, combinatorial experiments to find
synergistic biochemical, pharmacological and mechanical conditions for robust differentiation of bone marrow
MSCs into endothelial cells. (2) Perform an extensive evaluation of the synergistic role of mechanical stretch
and biochemical stimulation in differentiating bone marrow MSCs into vascular smooth muscle cells (vSMCs).
(3) Test the functionality and long-term differentiation of mechanically conditioned MSCs in enhancing
recellularized grafts for bypass surgeries. Together these studies will provide new insights into mechanically
mediated stem cell biology and provide optimized conditions for enhancing small diameter recellularized
vascular grafts.

## Key facts

- **NIH application ID:** 10129993
- **Project number:** 5R01HL141761-04
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Aaron Blair Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,250
- **Award type:** 5
- **Project period:** 2018-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129993

## Citation

> US National Institutes of Health, RePORTER application 10129993, Mechanical Conditioning of Mesenchymal Stem Cells for Enhanced Recellularized Vascular Grafts (5R01HL141761-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129993. Licensed CC0.

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