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Modular design of a tissue engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes.

Authors
  • Park, Jinkyu1
  • Anderson, Christopher W2
  • Sewanan, Lorenzo R3
  • Kural, Mehmet H4
  • Huang, Yan1
  • Luo, Jiesi1
  • Gui, Liqiong4
  • Riaz, Muhammad1
  • Lopez, Colleen A1
  • Ng, Ronald3
  • Das, Subhash K1
  • Wang, Juan4
  • Niklason, Laura5
  • Campbell, Stuart G3
  • Qyang, Yibing6
  • 1 Department of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, United States; Yale Stem Cell Center, 10 Amistad street, New Haven, CT 06511, United States; Vascular Biology and Therapeutics Program, Yale University, New Haven, CT 06510, United States. , (United States)
  • 2 Department of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, United States; Yale Stem Cell Center, 10 Amistad street, New Haven, CT 06511, United States; Vascular Biology and Therapeutics Program, Yale University, New Haven, CT 06510, United States; Department of Pathology, Yale University, New Haven, CT 06510, United States. , (United States)
  • 3 Department of Biomedical Engineering, Yale University, New Haven, CT 06510, United States. , (United States)
  • 4 Vascular Biology and Therapeutics Program, Yale University, New Haven, CT 06510, United States; Department of Anesthesiology, School of Medicine, Yale University, New Haven, CT 06511, United States. , (United States)
  • 5 Yale Stem Cell Center, 10 Amistad street, New Haven, CT 06511, United States; Vascular Biology and Therapeutics Program, Yale University, New Haven, CT 06510, United States; Department of Biomedical Engineering, Yale University, New Haven, CT 06510, United States; Department of Anesthesiology, School of Medicine, Yale University, New Haven, CT 06511, United States. , (United States)
  • 6 Department of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, United States; Yale Stem Cell Center, 10 Amistad street, New Haven, CT 06511, United States; Vascular Biology and Therapeutics Program, Yale University, New Haven, CT 06510, United States; Department of Pathology, Yale University, New Haven, CT 06510, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Acta biomaterialia
Publication Date
Jan 15, 2020
Volume
102
Pages
220–230
Identifiers
DOI: 10.1016/j.actbio.2019.10.019
PMID: 31634626
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Single ventricle heart defects (SVDs) are congenital disorders that result in a variety of complications, including increased ventricular mechanical strain and mixing of oxygenated and deoxygenated blood, leading to heart failure without surgical intervention. Corrective surgery for SVDs are traditionally handled by the Fontan procedure, requiring a vascular conduit for completion. Although effective, current conduits are limited by their inability to aid in pumping blood into the pulmonary circulation. In this report, we propose an innovative and versatile design strategy for a tissue engineered pulsatile conduit (TEPC) to aid circulation through the pulmonary system by producing contractile force. Several design strategies were tested for production of a functional TEPC. Ultimately, we found that porcine extracellular matrix (ECM)-based engineered heart tissue (EHT) composed of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and primary cardiac fibroblasts (HCF) wrapped around decellularized human umbilical artery (HUA) made an efficacious basal TEPC. Importantly, the TEPCs showed effective electrical and mechanical function. Initial pressure readings from our TEPC in vitro (0.68 mmHg) displayed efficient electrical conductivity enabling them to follow electrical pacing up to a 2 Hz frequency. This work represents a proof of principle study for our current TEPC design strategy. Refinement and optimization of this promising TEPC design will lay the groundwork for testing the construct's therapeutic potential in the future. Together this work represents a progressive step toward developing an improved treatment for SVD patients. STATEMENT OF SIGNIFICANCE: Single Ventricle Cardiac defects (SVD) are a form of congenital disorder with a morbid prognosis without surgical intervention. These patients are treated through the Fontan procedure which requires vascular conduits to complete. Fontan conduits have been traditionally made from stable or biodegradable materials with no pumping activity. Here, we propose a tissue engineered pulsatile conduit (TEPC) for use in Fontan circulation to alleviate excess strain in SVD patients. In contrast to previous strategies for making a pulsatile Fontan conduit, we employ a modular design strategy that allows for the optimization of each component individually to make a standalone tissue. This work sets the foundation for an in vitro, trainable human induced pluripotent stem cell based TEPC. Copyright © 2019. Published by Elsevier Ltd.

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