{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rossler KJ"],"funding":["National Science Foundation Graduate Research Fellowship Program","NHLBI Division of Intramural Research","NIH Office of the Director","NHLBI NIH HHS","Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison","NCI NIH HHS","NIGMS NIH HHS","NIH HHS"],"pagination":["e172168"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10906451"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_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 with 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 affects the properties of resulting hiPSC-ECTs. Therefore, hiPSC-CMs were differentiated and purified using either lactate-based media or MACS. Global proteomics revealed that lactate-purified hiPSC-CMs displayed a differential phenotype over MACS hiPSC-CMs. hiPSC-CMs were then integrated into 3D hiPSC-ECTs and cultured for 4 weeks. Structurally, there was no significant difference in sarcomere length between lactate and MACS hiPSC-ECTs. Assessment of isometric twitch force and Ca2+ transient measurements revealed similar functional performance between purification methods. High-resolution mass spectrometry-based quantitative proteomics showed no significant difference in protein pathway expression or myofilament proteoforms. Taken together, this study demonstrates that lactate- and MACS-purified hiPSC-CMs generate ECTs with comparable structural, functional, and proteomic features, and it suggests that lactate purification does not result in an irreversible change in a hiPSC-CM phenotype."],"journal":["JCI insight"],"pubmed_title":["Lactate- and immunomagnetic-purified hiPSC-derived cardiomyocytes generate comparable engineered cardiac tissue constructs."],"pmcid":["PMC10906451"],"funding_grant_id":["R01 HL109810","S10OD018475","R01 GM125085",". DGE-1747503","S10 OD018475","P30 CA014520","S10 OD023526","U01 HL134764","R01 HL096971"],"pubmed_authors":["Kim G","Zhang J","Zhu Y","Aballo TJ","Farrell ET","Ralphe JC","Mann MW","Bayne EF","Kamp TJ","Rossler KJ","Ge Y","de Lange WJ","Melby JA"],"additional_accession":[]},"is_claimable":false,"name":"Lactate- and immunomagnetic-purified hiPSC-derived cardiomyocytes generate comparable engineered cardiac tissue constructs.","description":"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 with 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 affects the properties of resulting hiPSC-ECTs. Therefore, hiPSC-CMs were differentiated and purified using either lactate-based media or MACS. Global proteomics revealed that lactate-purified hiPSC-CMs displayed a differential phenotype over MACS hiPSC-CMs. hiPSC-CMs were then integrated into 3D hiPSC-ECTs and cultured for 4 weeks. Structurally, there was no significant difference in sarcomere length between lactate and MACS hiPSC-ECTs. Assessment of isometric twitch force and Ca2+ transient measurements revealed similar functional performance between purification methods. High-resolution mass spectrometry-based quantitative proteomics showed no significant difference in protein pathway expression or myofilament proteoforms. Taken together, this study demonstrates that lactate- and MACS-purified hiPSC-CMs generate ECTs with comparable structural, functional, and proteomic features, and it suggests that lactate purification does not result in an irreversible change in a hiPSC-CM phenotype.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan","modification":"2025-04-04T20:40:53.7Z","creation":"2025-04-04T20:40:53.7Z"},"accession":"S-EPMC10906451","cross_references":{"pubmed":["37988170"],"doi":["10.1172/jci.insight.172168"]}}