{"doi":"10.1038/s41598-021-89478-9","title":"A predictive in vitro risk assessment platform for pro-arrhythmic toxicity using human 3D cardiac microtissues","abstract":"Cardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.","journal":"Scientific Reports","year":2021,"id":159362,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":332035,"name":"Tae Yun Kim","orcid":"0000-0003-0605-9575","position":1,"is_corresponding":false},{"id":347521,"name":"Fabiola Munarin","orcid":"0000-0002-6949-0162","position":2,"is_corresponding":false},{"id":661483,"name":"Arvin H. Soepriatna","orcid":"0000-0002-7756-1389","position":3,"is_corresponding":false},{"id":347522,"name":"Rajeev J. Kant","orcid":"0000-0002-3067-5880","position":4,"is_corresponding":false},{"id":669869,"name":"Ulrike Mende","orcid":"0000-0002-3362-6072","position":5,"is_corresponding":false},{"id":332049,"name":"Bum‐Rak Choi","orcid":"0000-0001-7319-3219","position":6,"is_corresponding":false},{"id":347524,"name":"Kareen L. K. Coulombe","orcid":"0000-0001-6664-339X","position":7,"is_corresponding":false},{"id":669868,"name":"Celinda M. Kofron","orcid":"0000-0003-4608-5989","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":null,"created_at":"2026-07-18T23:44:35.165422Z","pmid":"33986332","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}