human engineered heart tissue as a versatile tool in basic research and preclinical toxicology人类工程心脏组织作为一个通用的工具在基础研究和临床前毒理学.pdfVIP

Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology 1 1 2 1 ¨ 1 1 Sebastian Schaaf , Aya Shibamiya , Marco Mewe , Alexandra Eder , Andrea Stohr , Marc N. Hirt , 1 1¤ 3 1. Thomas Rau , Wolfram-Hubertus Zimmermann , Lenard Conradi , Thomas Eschenhagen , Arne 1 . Hansen * 1 Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 2 Department of Pharmacology for Pharmacists, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 3 Department of Cardiovascular Surgery, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Abstract Human embryonic stem cell (hESC) progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available as in the case of cardiomyocytes. However, high content experimental platforms are lacking that allow the function of hESC-derived cardiomyocytes to be studied under relatively physiological and standardized conditions. Here we describe a simple and robust protocol for the generation of fibrin-based human engineered heart tissue (hEHT) in a 24-well format using an unselected population of differentiated human embryonic stem cells containing 30–40% a-actinin-positive cardiac myocytes. Human EHTs started to show coherent contractions 5–10 days after casting, reached regular (mean 0.5 Hz) and stron