{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T21:04:46Z","timestamp":1740171886061,"version":"3.37.3"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010345","name":"B. Braun-Foundation","doi-asserted-by":"crossref","award":["154-2013"],"award-info":[{"award-number":["154-2013"]}],"id":[{"id":"10.13039\/100010345","id-type":"DOI","asserted-by":"crossref"}]},{"name":"K\u00f6ln Fortune","award":["154-2013"],"award-info":[{"award-number":["154-2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2019,3,6]]},"abstract":"<jats:p><jats:italic>Aims<\/jats:italic>. Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) have become a promising tool in cardiovascular safety pharmacology. Immaturity of iPS-CMs remains an ongoing concern. We compared electrophysiological and contractile features of cardiac bodies (hiPS-CBs) derived from human-induced pluripotent stem cells and human neonatal and infantile myocardial slices relevant for drug screening. <jats:italic>Methods and Results<\/jats:italic>. Myocardial tissue slices were prepared from biopsies obtained from patients undergoing surgery for hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). Electrophysiological features and response to I<jats:sub>k,r<\/jats:sub> blockade as well as contractile properties were investigated using microelectrodes and isometric force measurements and were compared to hiPS-CBs. Both native myocardial tissue slices as well as hiPS-CBs showed action potential prolongation after I<jats:sub>k,r<\/jats:sub> blockade, but early afterdepolarisations could be observed in native myocardial tissue slices only. The force-frequency relationship (FFR) varied at lower frequencies and was negative throughout at higher frequencies in hiPS-CBs. In contrast, native myocardial tissue slices exhibited positive, negative, and biphasic FFRs. In contrast to native myocardial tissue slices, hiPS-CBs failed to show an inotropic response to <jats:italic>\u00df<\/jats:italic>-adrenergic stimulation. Although all groups showed <jats:italic>\u00df<\/jats:italic>-adrenergic induced positive lusitropy, the effect was more pronounced in myocardial tissue slices. <jats:italic>Conclusion<\/jats:italic>. hiPS-CBs were able to reproduce AP prolongation after I<jats:sub>k,r<\/jats:sub> blockade, but to a lesser extent compared to human neonatal and infantile myocardial tissue slices. Early afterdepolarisations could not be induced in hiPS-CBs. Contractile force was differently regulated by <jats:italic>\u03b2<\/jats:italic>-adrenergic stimulation in hiPS-CBs and the native myocardium. If used for cardiotoxicity screening, caution is warranted as hiPS-CBs might be less sensitive to pharmacologic targets compared to the native myocardium of neonates and infants.<\/jats:p>","DOI":"10.1155\/2019\/6096294","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T18:41:51Z","timestamp":1551897711000},"page":"1-14","source":"Crossref","is-referenced-by-count":5,"title":["Different Responses to Drug Safety Screening Targets between Human Neonatal and Infantile Heart Tissue and Cardiac Bodies Derived from Human-Induced Pluripotent Stem Cells"],"prefix":"10.1155","volume":"2019","author":[{"given":"Jan","family":"Trieschmann","sequence":"first","affiliation":[{"name":"Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpener Str. 52, 50924 Cologne, Germany"},{"name":"Institute for Neurophysiology, University of Cologne, Robert-Koch-Str. 39, 50931 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz","family":"Haustein","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpener Str. 52, 50924 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"K\u00f6ster","sequence":"additional","affiliation":[{"name":"Institute for Neurophysiology, University of Cologne, Robert-Koch-Str. 39, 50931 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Hescheler","sequence":"additional","affiliation":[{"name":"Institute for Neurophysiology, University of Cologne, Robert-Koch-Str. 39, 50931 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad","family":"Brockmeier","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of 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