# Development of HLA engineered universal vascular grafts from human iPSCs

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $418,750

## Abstract

Access to readily available small diameter (2-4 mm) vascular grafts presents an unmet need to patients following
peripheral arterial injury or peripheral arterial atherosclerosis. Although prosthetic or autologous grafts could be
utilized for this purpose, the potential risk of infection or thrombus formation in prosthetic grafts and the limited
autologous vessel availability in a subset of patients arising from disease, prior utilization, or size mismatch to
the injured vessel restricts their application. Acellular tissue engineered vascular grafts (TEVGs) derived from
human induced pluripotent stem cells (hiPSCs) provide a promising alternative to autologous or synthetic grafts.
These hiPSC-TEVGs can be constructed from vascular smooth muscle cells (VSMCs) and endothelial cells
(ECs) derived from hiPSCs and have previously been shown to have mechanical properties comparable to native
vessels used in clinical bypass surgeries. hiPSC-TEVGs offer several advantages over other vascular grafts,
notably the ability for hiPSCs to self-renew and differentiate into almost every cell type in the body allows for a
replenishable source from which to derive VSMCs to reproducibly create TEVGs. Critically, hiPSC-TEVGs could
be utilized to address the unmet needs of readily available small diameter vascular grafts for peripheral arterial
injury or atherosclerosis through decellularization followed by endothelialization of the TEVG. Whereas acellular
TEVGs could directly be implemented as larger diameter vascular grafts, small diameter grafts require an
endothelium to prevent thrombosis in the vessel. This fact further increases the value of the hiPSC technology
due to the successful derivation of hypoimmunogenic, “universal” ECs for this purpose. Hypoimmunogenic
hiPSCs are created through modulating the expression of human leukocyte antigens (HLAs) so as to avoid
destruction by the host immune system, while providing a healthy endothelium to small diameter grafts. Creation
and investigation of the biomaterial and cellular interactions of mechanically robust, hypoimmunogenic,
endothelialized hiPSC-TEVGs forms the basis of this proposal, and success here will increase the economic and
practical impact of the product through enhancing short term storage capability and reaching an expansive
patient populace. In pursuit of this, expansive validation and characterization will be done on hypoimmunogenic,
universal EC differentiation to produce functionally and mechanically robust ECs for graft engineering.
Decellularized, hypoimmunogenic endothelialized hiPSC-TEVGs will also be generated and biocompatibility of
platelet- and whole blood-luminal surface interactions will be assessed. Further, in vivo immunocompatibility and
therapeutic efficacy of universal hiPSC-TEVGs will be evaluated in a humanized rat aortic interposition graft
model. Information gleaned from this proposal will demonstrate the diversity and practicality of the universal
hiPSC-TEVG technology, and ...

## Key facts

- **NIH application ID:** 10457467
- **Project number:** 5R01HL155411-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Yibing Qyang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457467

## Citation

> US National Institutes of Health, RePORTER application 10457467, Development of HLA engineered universal vascular grafts from human iPSCs (5R01HL155411-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10457467. Licensed CC0.

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