# Readily Available Stem Cell-Based Vascular Grafts for Emergent Surgical Care

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $61,871

## Abstract

Project Summary
Tissue engineered vascular grafts (TEVGs) for traumatic vascular injury repair in small diameter (2-
4mm) vessels can be made from human induced pluripotent stem cell derived vascular smooth
muscle cells (hiPSC-VSMC) seeded onto a polyglycolic acid (PGA) scaffold. Furthermore, these
TEVGs can be subsequently decellularized and stored long term for use in acute care for traumatic
injury. For larger diameter vessel repair, it is adequate to implant an acellular scaffold and allow host
cells to migrate from anastomotic edges to line the implanted vessel lumen. However, this model is
not effective for smaller diameter vessels that are more prone to thrombosis. Researchers have
attempted to solve this problem by coating the lumen of implanted vessels with endothelial cells
(ECs) prior to implantation. However, data from implanted grafts suggests there is a short turnover
time for implanted EC populations within these grafts. In the case of elderly or diseased patients,
they may not retain quality EC function. Therefore, this patient population may display poor
integration of host cells into the implanted tissue, which may lead to an increased risk of thrombotic
and stenotic events. The purpose of this project is to generate a stable hiPSC line with controllable
expression of the pro-survival factor Bcl-2 to generate hiPSC derived endothelial cells (hiPSC-ECs)
as a readily available cell source to line the lumen of decellularized TEVGs prior to implantation. A
stable hiPSC line with doxycycline inducible expression of the pro-survival factor Bcl-2 will be
generated via transcription activator-like effector nucleases (TALEN) gene editing. Additionally, a
robust “safety switch” system using ectopically expressed thymidine kinase (TK) will be employed to
ensure cells may be removed post implantation should unwanted effects occur. Decellularized
TEVGs will have their lumen coated with hiPSC-ECs made from this gene edited Bcl-2+TK+ cell line.
These endothelialized TEVGs will undergo fluid shear stress training to enhance hiPSC-EC function
prior to implantation into an immunocompromised rat model as an aortic interposition graft to test the
efficacy of this doxycycline inducible Bcl-2 system. This platform will allow for a readily available cell
line to be used to produce a long lasting hiPSC-EC lumen that can maintain patency of the graft as it
fully integrates with patients who may have subpar EC function.

## Key facts

- **NIH application ID:** 10414459
- **Project number:** 3R01HL150352-02S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Yibing Qyang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $61,871
- **Award type:** 3
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414459

## Citation

> US National Institutes of Health, RePORTER application 10414459, Readily Available Stem Cell-Based Vascular Grafts for Emergent Surgical Care (3R01HL150352-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10414459. Licensed CC0.

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