Fully biologic endothelialized-tissue-engineered vascular conduits provide antithrombotic function and graft patency

Jinkyu Park¹, Muhammad Riaz², Lingfeng Qin³, Wei Zhang², Luke Batty⁴, Saba Fooladi², Mehmet H Kural⁵, Xin Li², Hangqi Luo², Zhen Xu², Juan Wang⁵, Kimihiko Banno⁶, Sean X Gu⁷, Yifan Yuan⁵, Christopher W Anderson⁴, Matthew W Ellis⁸, Jiahui Zhou², Jiesi Luo², Xiangyu Shi², Jae Hun Shin⁹, Yufeng Liu¹⁰, Seoyeon Lee¹¹, Mervin C Yoder⁶, Robert W Elder¹², Michael Mak¹³, Stephanie Thorn¹⁴, Albert Sinusas¹⁴, Peter J Gruber¹⁵, John Hwa¹⁴, George Tellides¹⁶, Laura E Niklason¹⁷, Yibing Qyang¹⁸

Affiliations

¹ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Physiology, College of Medicine, Hallym University, Hallymdaehak-gil, Chuncheon-si 24252, Gangwon-Do, South Korea.
² Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA.
³ Department of Surgery, Yale University, New Haven, CT 06520, USA.
⁴ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
⁵ Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA.
⁶ Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁷ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Department of Laboratory Medicine, Yale University, New Haven, CT 06519, USA.
⁸ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06519, USA.
⁹ Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA.
¹⁰ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Yale Biological and Biomedical Sciences, Graduate School of Arts and Sciences, Yale University, New Haven, CT 06511, USA.
¹¹ Yale Biological and Biomedical Sciences, Graduate School of Arts and Sciences, Yale University, New Haven, CT 06511, USA.
¹² Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Department of Pediatrics, Yale School of Medicine, New Haven, CT 06520, USA.
¹³ Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA.
¹⁴ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
¹⁵ Department of Surgery, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
¹⁶ Department of Surgery, Yale University, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
¹⁷ Yale Stem Cell Center, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA.
¹⁸ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA. Electronic address: yibing.qyang@yale.edu.

PMID: 39644899
PMCID: PMC11698629 (available on 2026-01-02)
DOI: 10.1016/j.stem.2024.11.006

Fully biologic endothelialized-tissue-engineered vascular conduits provide antithrombotic function and graft patency

Jinkyu Park et al. Cell Stem Cell. 2025.

. 2025 Jan 2;32(1):137-143.e6.

doi: 10.1016/j.stem.2024.11.006. Epub 2024 Dec 6.

Authors

Affiliations

¹ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Physiology, College of Medicine, Hallym University, Hallymdaehak-gil, Chuncheon-si 24252, Gangwon-Do, South Korea.
² Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA.
³ Department of Surgery, Yale University, New Haven, CT 06520, USA.
⁴ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
⁵ Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA.
⁶ Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁷ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Department of Laboratory Medicine, Yale University, New Haven, CT 06519, USA.
⁸ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06519, USA.
⁹ Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA.
¹⁰ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Yale Biological and Biomedical Sciences, Graduate School of Arts and Sciences, Yale University, New Haven, CT 06511, USA.
¹¹ Yale Biological and Biomedical Sciences, Graduate School of Arts and Sciences, Yale University, New Haven, CT 06511, USA.
¹² Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Department of Pediatrics, Yale School of Medicine, New Haven, CT 06520, USA.
¹³ Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA.
¹⁴ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
¹⁵ Department of Surgery, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
¹⁶ Department of Surgery, Yale University, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
¹⁷ Yale Stem Cell Center, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA.
¹⁸ Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA. Electronic address: yibing.qyang@yale.edu.

PMID: 39644899
PMCID: PMC11698629 (available on 2026-01-02)
DOI: 10.1016/j.stem.2024.11.006

Abstract

Tissue-engineered vascular conduits (TEVCs), often made by seeding autologous bone marrow cells onto biodegradable polymeric scaffolds, hold promise toward treating single-ventricle congenital heart defects (SVCHDs). However, the clinical adoption of TEVCs has been hindered by a high incidence of graft stenosis in prior TEVC clinical trials. Herein, we developed endothelialized TEVCs by coating the luminal surface of decellularized human umbilical arteries with human induced pluripotent stem cell (hiPSC)-derived endothelial cells (ECs), followed by shear stress training, in flow bioreactors. These TEVCs provided immediate antithrombotic function and expedited host EC recruitment after implantation as interposition inferior vena cava grafts in nude rats. Graft patency was maintained with no thrombus formation, followed by complete replacement of host ECs. Our study lays the foundation for future production of fully biologic TEVCs composed of hiPSC-derived ECs as an innovative therapy for SVCHDs.

Keywords: endothelial cell; flow bioreactor; human induced pluripotent stem cell; shear stress training; single ventricle congenital heart defect; tissue-engineered vascular conduit.

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Conflict of interest statement

Declaration of interests L.E.N. is a founder and shareholder in Humacyte, Inc. Humacyte generates engineered blood vessels using smooth muscle cells. L.E.N.’s spouse has equity in Humacyte and L.E.N. serves on Humacyte’s board of directors. L.E.N. is an inventor on patents licensed to Humacyte and generating royalties. Humacyte did not support these studies or influence conduct, description, or interpretation of research in this manuscript. A patent application has been submitted based on the findings of this manuscript.

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Fully biologic endothelialized-tissue-engineered vascular conduits provide antithrombotic function and graft patency

Affiliations

Fully biologic endothelialized-tissue-engineered vascular conduits provide antithrombotic function and graft patency

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Abstract

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