Modular design of a tissue engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes
Modular design of a tissue engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes
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DOI：
10.1016/j.actbio.2019.10.019
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发表时间：
2020-01-15
影响因子：
9.7
通讯作者：
Qyang, Yibing
中科院分区：
文献类型：
--
作者：
Park, Jinkyu;Anderson, Christopher W.;Qyang, Yibing
单心室心脏缺陷（SVDs）是一种先天性疾病，可导致各种并发症，包括心室机械应变增加以及含氧和脱氧血液混合，导致心力衰竭而无需手术干预。SVD的矫正手术传统上由Fontan手术处理，需要血管管道完成。虽然有效，但电流导管受限于它们不能帮助将血液泵入肺循环。在这份报告中，我们提出了一个创新的和多功能的设计策略，组织工程脉动导管（TEPC），以帮助通过肺系统产生收缩力循环。几种设计策略进行了测试的功能TEPC的生产。最终，我们发现基于猪细胞外基质（ECM）的工程化心脏组织（EHT）由人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）和原代心脏成纤维细胞（HCF）组成，包裹在脱细胞的人脐动脉（HUA）周围，形成有效的基础TEPC。重要的是，TEPC显示出有效的电气和机械功能。体外TEPC的初始压力读数（0.68 mmHg）显示出有效的电导率，使其能够跟踪高达2 Hz频率的电起搏。这项工作是我们目前的TEPC设计策略的原理研究的证明。这种有前途的TEPC设计的改进和优化将为将来测试该结构的治疗潜力奠定基础。总之，这项工作代表了一个进步的一步，朝着发展一个改进的治疗SVD patients.Statement的重要性单支心脏缺陷（SVD）是一种先天性疾病的病态预后没有手术干预。这些患者通过Fontan手术进行治疗，该手术需要血管导管来完成。Fontan导管传统上由稳定或可生物降解的材料制成，没有泵送活性。在这里，我们提出了一种组织工程脉动导管（TEPC）用于Fontan循环，以减轻SVD患者的过度应变。与先前用于制造脉动Fontan导管的策略相比，我们采用模块化设计策略，该策略允许单独优化每个组件以制造独立组织。这项工作为体外可训练的基于人诱导多能干细胞的TEPC奠定了基础。(C)2019 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
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 significanceSingle 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. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.