{"id":6484,"date":"2023-02-17T06:49:13","date_gmt":"2023-02-17T06:49:13","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2021-anthracycline-induced-cardiotoxicity-molecular-insights-obtained-from-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-hipsc-cms\/"},"modified":"2023-02-17T06:49:14","modified_gmt":"2023-02-17T06:49:14","slug":"2021-anthracycline-induced-cardiotoxicity-molecular-insights-obtained-from-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-hipsc-cms","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2021-anthracycline-induced-cardiotoxicity-molecular-insights-obtained-from-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-hipsc-cms\/","title":{"rendered":"2021 &#8211; Anthracycline-Induced Cardiotoxicity: Molecular Insights Obtained from Human-Induced Pluripotent Stem Cell\u2013Derived Cardiomyocytes (hiPSC-CMs)"},"content":{"rendered":"<p>Anthracyclines are a class of chemotherapy drugs that are highly effective for\u00a0the treatment of human cancers, but their clinical use is limited by associated dose-dependent\u00a0cardiotoxicity. The precise mechanisms by which individual anthracycline induces\u00a0cardiotoxicity are not fully understood. Human-induced pluripotent stem cell\u2013derived\u00a0cardiomyocytes (hiPSC-CMs) are emerging as a physiologically relevant model to assess\u00a0drugs cardiotoxicity. Here, we describe an assay platform by coupling hiPSC-CMs and\u00a0impedance measurement, which allows real-time monitoring of cardiomyocyte cellular index,\u00a0beating amplitude, and beating rate. Using this approach, we have performed comparative\u00a0studies on a panel of four anthracycline drugs (doxorubicin, epirubicin, idarubicin, and\u00a0daunorubicin) which share a high degree of structural similarity but are associated with\u00a0distinct cardiotoxicity profiles and maximum cumulative dose limits. Notably, results from our\u00a0hiPSC-CMs impedance model (dose-dependent responses and EC<sub>50<\/sub> values) agree well with\u00a0the recommended clinical dose limits for these drugs. Using time-lapse imaging and RNAseq,\u00a0we found that the differences in anthracycline cardiotoxicity are closely linked to extent of\u00a0cardiomyocyte uptake and magnitude of activation\/inhibition of several cellular pathways\u00a0such as death receptor signaling, ROS production, and dysregulation of calcium signaling.\u00a0The results provide molecular insights into anthracycline cardiac interactions and offer a\u00a0novel assay system to more robustly assess potential cardiotoxicity during drug development.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[77],"therapeutic_areas":[54],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-6484","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6484","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6484"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6484"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6484"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6484"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6484"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6484"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6484"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6484"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6484"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}