Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model

Author:

Riegler Johannes1,Tiburcy Malte1,Ebert Antje1,Tzatzalos Evangeline1,Raaz Uwe1,Abilez Oscar J.1,Shen Qi1,Kooreman Nigel G.1,Neofytou Evgenios1,Chen Vincent C.1,Wang Mouer1,Meyer Tim1,Tsao Philip S.1,Connolly Andrew J.1,Couture Larry A.1,Gold Joseph D.1,Zimmermann Wolfram H.1,Wu Joseph C.1

Affiliation:

1. From the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular...

Abstract

Rationale: Tissue engineering approaches may improve survival and functional benefits from human embryonic stem cell–derived cardiomyocyte transplantation, thereby potentially preventing dilative remodeling and progression to heart failure. Objective: Assessment of transport stability, long-term survival, structural organization, functional benefits, and teratoma risk of engineered heart muscle (EHM) in a chronic myocardial infarction model. Methods and Results: We constructed EHMs from human embryonic stem cell–derived cardiomyocytes and released them for transatlantic shipping following predefined quality control criteria. Two days of shipment did not lead to adverse effects on cell viability or contractile performance of EHMs (n=3, P =0.83, P =0.87). One month after ischemia/reperfusion injury, EHMs were implanted onto immunocompromised rat hearts to simulate chronic ischemia. Bioluminescence imaging showed stable engraftment with no significant cell loss between week 2 and 12 (n=6, P =0.67), preserving ≤25% of the transplanted cells. Despite high engraftment rates and attenuated disease progression (change in ejection fraction for EHMs, −6.7±1.4% versus control, −10.9±1.5%; n>12; P =0.05), we observed no difference between EHMs containing viable and nonviable human cardiomyocytes in this chronic xenotransplantation model (n>12; P =0.41). Grafted cardiomyocytes showed enhanced sarcomere alignment and increased connexin 43 expression at 220 days after transplantation. No teratomas or tumors were found in any of the animals (n=14) used for long-term monitoring. Conclusions: EHM transplantation led to high engraftment rates, long-term survival, and progressive maturation of human cardiomyocytes. However, cell engraftment was not correlated with functional improvements in this chronic myocardial infarction model. Most importantly, the safety of this approach was demonstrated by the lack of tumor or teratoma formation.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Physiology

Cited by 203 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3