{"doi":"10.1101/2023.05.05.539642","title":"Lactate and Immunomagnetic-purified iPSC-derived Cardiomyocytes Generate Comparable Engineered Cardiac Tissue Constructs","abstract":"Abstract Three-dimensional engineered cardiac tissue (ECT) using purified human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) has emerged as an appealing model system for the study of human cardiac biology and disease. A recent study reported widely-used metabolic (lactate) purification of monolayer hiPSC-CM cultures results in an ischemic cardiomyopathy-like phenotype compared to magnetic antibody-based cell sorting (MACS) purification, complicating the interpretation of studies using lactate-purified hiPSC-CMs. Herein, our objective was to determine if use of lactate relative to MACs-purified hiPSC-CMs impacts the properties of resulting hiPSC-ECTs. Therefore, hiPSC-CMs were differentiated and purified using either lactate-based media or MACS. After purification, hiPSC-CMs were combined with hiPSC-cardiac fibroblasts to create 3D hiPSC-ECT constructs maintained in culture for four weeks. There were no structural differences observed, and there was no significant difference in sarcomere length between lactate and MACS hiPSC-ECTs. Assessment of isometric twitch force, Ca 2+ transients, and β-adrenergic response revealed similar functional performance between purification methods. High-resolution mass spectrometry (MS)-based quantitative proteomics showed no significant difference in any protein pathway expression or myofilament proteoforms. Taken together, this study demonstrates lactate- and MACS-purified hiPSC-CMs generate ECTs with comparable molecular and functional properties, and suggests lactate purification does not result in an irreversible change in hiPSC-CM phenotype. Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":407016,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.945,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":275526,"name":"Willem J. de Lange","orcid":"0000-0001-7296-8924","position":1,"is_corresponding":false},{"id":494350,"name":"Morgan Mann","orcid":"0000-0001-6623-9522","position":2,"is_corresponding":false},{"id":347400,"name":"Timothy J. Aballo","orcid":"0000-0003-1164-5966","position":3,"is_corresponding":false},{"id":298235,"name":"Jake A. Melby","orcid":"0000-0003-1499-9508","position":4,"is_corresponding":false},{"id":20466,"name":" Jianhua Zhang","orcid":"0000-0002-3819-2437","position":5,"is_corresponding":false},{"id":520759,"name":"Gina Kim","orcid":"0000-0002-4389-8653","position":6,"is_corresponding":false},{"id":275524,"name":"Elizabeth F. Bayne","orcid":"0000-0002-6252-2934","position":7,"is_corresponding":false},{"id":301519,"name":"Yanlong Zhu","orcid":"0000-0003-4909-7336","position":8,"is_corresponding":false},{"id":406383,"name":"Emily T. Farrell","orcid":"0000-0003-2058-2397","position":9,"is_corresponding":false},{"id":275534,"name":"Timothy J. Kamp","orcid":"0000-0003-2103-7876","position":10,"is_corresponding":false},{"id":275533,"name":"J. Carter Ralphe","orcid":"0000-0001-8116-2324","position":11,"is_corresponding":false},{"id":256465,"name":"Ying Ge","orcid":"0000-0001-5211-6812","position":12,"is_corresponding":false},{"id":1038957,"name":"Kalina J. Rossler","orcid":"0000-0003-0353-1774","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:21:07.213041Z","pmid":"37205556","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":[]}