{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Prondzynski M"],"funding":["NCATS NIH HHS","NHLBI NIH HHS"],"pubmed_abstract":["In the last decade human iPSC-derived cardiomyocytes (hiPSC-CMs) proved to be valuable for cardiac disease modeling and cardiac regeneration, yet challenges with scale, quality, inter-batch consistency, and cryopreservation remain, reducing experimental reproducibility and limiting clinical translation. Here, we report a robust cardiac differentiation protocol that uses Wnt modulation and a stirred suspension bioreactor to produce on average 124 million hiPSC-CMs with >90% purity using a variety of hiPSC lines (19 differentiations; 10 iPSC lines). After controlled freeze and thaw, bioreactor-derived CMs (bCMs) showed high viability (>90%), interbatch reproducibility in cellular morphology, function, drug response and ventricular identity, which was further supported by single cell transcriptomes. bCMs on microcontact printed substrates revealed a higher degree of sarcomere maturation and viability during long-term culture compared to monolayer-derived CMs (mCMs). Moreover, functional investigation of bCMs in 3D engineered heart tissues showed earlier and stronger force production during long-term culture, and robust pacing capture up to 4 Hz when compared to mCMs. bCMs derived from this differentiation protocol will expand the applications of hiPSC-CMs by providing a reproducible, scalable, and resource efficient method to generate cardiac cells with well-characterized structural and functional properties superior to standard mCMs."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.02.24.581789"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10925150"],"repository":["biostudies-literature"],"pubmed_title":["Efficient and reproducible generation of human iPSC-derived cardiomyocytes using a stirred bioreactor."],"pmcid":["PMC10925150"],"funding_grant_id":["UH3 HL141798","UH3 TR003279"],"pubmed_authors":["Trembley MA","Milosh JB","Pu WT","Berkson P","Sweat ME","Anyanwu NJ","Prondzynski M","Bortolin RH","Cordoves AM","Bezzerides VJ","Tharani Y","Liu X","Shani K","Mayourian J","Zhang Y","Walker D","Parker KK","Cotton J","Liu F"],"additional_accession":[]},"is_claimable":false,"name":"Efficient and reproducible generation of human iPSC-derived cardiomyocytes using a stirred bioreactor.","description":"In the last decade human iPSC-derived cardiomyocytes (hiPSC-CMs) proved to be valuable for cardiac disease modeling and cardiac regeneration, yet challenges with scale, quality, inter-batch consistency, and cryopreservation remain, reducing experimental reproducibility and limiting clinical translation. Here, we report a robust cardiac differentiation protocol that uses Wnt modulation and a stirred suspension bioreactor to produce on average 124 million hiPSC-CMs with >90% purity using a variety of hiPSC lines (19 differentiations; 10 iPSC lines). After controlled freeze and thaw, bioreactor-derived CMs (bCMs) showed high viability (>90%), interbatch reproducibility in cellular morphology, function, drug response and ventricular identity, which was further supported by single cell transcriptomes. bCMs on microcontact printed substrates revealed a higher degree of sarcomere maturation and viability during long-term culture compared to monolayer-derived CMs (mCMs). Moreover, functional investigation of bCMs in 3D engineered heart tissues showed earlier and stronger force production during long-term culture, and robust pacing capture up to 4 Hz when compared to mCMs. bCMs derived from this differentiation protocol will expand the applications of hiPSC-CMs by providing a reproducible, scalable, and resource efficient method to generate cardiac cells with well-characterized structural and functional properties superior to standard mCMs.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2025-04-04T20:18:24.995Z","creation":"2025-04-04T20:18:24.995Z"},"accession":"S-EPMC10925150","cross_references":{"pubmed":["38464269"],"doi":["10.1101/2024.02.24.581789"]}}