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Article: Human Cardiac Ventricular‐Like Organoid Chambers and Tissue Strips From Pluripotent Stem Cells as a Two‐Tiered Assay for Inotropic Responses

TitleHuman Cardiac Ventricular‐Like Organoid Chambers and Tissue Strips From Pluripotent Stem Cells as a Two‐Tiered Assay for Inotropic Responses
Authors
KeywordsMyocytes
Cardiac
Induced Pluripotent Stem Cells
Cardiomyocytes CMs
Issue Date2019
PublisherAmerican Society for Clinical Pharmacology and Therapeutics. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1532-6535/issues
Citation
Clinical Pharmacology and Therapeutics, 2019, v. 106 n. 2, p. 402-414 How to Cite?
AbstractTraditional drug discovery is an inefficient process. Human pluripotent stem cell‐derived cardiomyocytes can potentially fill the gap between animal and clinical studies, but conventional two‐dimensional cultures inadequately recapitulate the human cardiac phenotype. Here, we systematically examined the pharmacological responses of engineered human ventricular‐like cardiac tissue strips (hvCTS) and organoid chambers (hvCOC) to 25 cardioactive compounds covering various drug classes. While hvCTS effectively detected negative and null inotropic effects, the sensitivity to positive inotropes was modest. We further quantified the predictive capacity of hvCTS in a blinded screening, with accuracies for negative, positive, and null inotropic effects at 100%, 86%, and 80%, respectively. Interestingly, hvCOC, with a pro‐maturation milieu that yields physiologically complex parameters, displayed enhanced positive inotropy. Based on these results, we propose a two‐tiered screening system for avoiding false positives and negatives. Such an approach would facilitate drug discovery by leading to better overall success.
Persistent Identifierhttp://hdl.handle.net/10722/277433
ISSN
2017 Impact Factor: 6.544
2015 SCImago Journal Rankings: 2.414

 

DC FieldValueLanguage
dc.contributor.authorKeung, W-
dc.contributor.authorChan, PKW-
dc.contributor.authorBackeris, PC-
dc.contributor.authorLee, EK-
dc.contributor.authorWONG, N-
dc.contributor.authorWONG, AOT-
dc.contributor.authorWong, KYG-
dc.contributor.authorChan, CWY-
dc.contributor.authorFermini, B-
dc.contributor.authorCosta, KD-
dc.contributor.authorLi, RA-
dc.date.accessioned2019-09-20T08:50:58Z-
dc.date.available2019-09-20T08:50:58Z-
dc.date.issued2019-
dc.identifier.citationClinical Pharmacology and Therapeutics, 2019, v. 106 n. 2, p. 402-414-
dc.identifier.issn0009-9236-
dc.identifier.urihttp://hdl.handle.net/10722/277433-
dc.description.abstractTraditional drug discovery is an inefficient process. Human pluripotent stem cell‐derived cardiomyocytes can potentially fill the gap between animal and clinical studies, but conventional two‐dimensional cultures inadequately recapitulate the human cardiac phenotype. Here, we systematically examined the pharmacological responses of engineered human ventricular‐like cardiac tissue strips (hvCTS) and organoid chambers (hvCOC) to 25 cardioactive compounds covering various drug classes. While hvCTS effectively detected negative and null inotropic effects, the sensitivity to positive inotropes was modest. We further quantified the predictive capacity of hvCTS in a blinded screening, with accuracies for negative, positive, and null inotropic effects at 100%, 86%, and 80%, respectively. Interestingly, hvCOC, with a pro‐maturation milieu that yields physiologically complex parameters, displayed enhanced positive inotropy. Based on these results, we propose a two‐tiered screening system for avoiding false positives and negatives. Such an approach would facilitate drug discovery by leading to better overall success.-
dc.languageeng-
dc.publisherAmerican Society for Clinical Pharmacology and Therapeutics. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1532-6535/issues-
dc.relation.ispartofClinical Pharmacology and Therapeutics-
dc.subjectMyocytes-
dc.subjectCardiac-
dc.subjectInduced Pluripotent Stem Cells-
dc.subjectCardiomyocytes CMs-
dc.titleHuman Cardiac Ventricular‐Like Organoid Chambers and Tissue Strips From Pluripotent Stem Cells as a Two‐Tiered Assay for Inotropic Responses-
dc.typeArticle-
dc.identifier.emailKeung, W: wkeung@hku.hk-
dc.identifier.emailLi, RA: ronaldli@hkucc.hku.hk-
dc.identifier.authorityKeung, W=rp01887-
dc.identifier.authorityChan, CWY=rp01311-
dc.identifier.authorityLi, RA=rp01352-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/cpt.1385-
dc.identifier.pmid30723889-
dc.identifier.scopuseid_2-s2.0-85063451293-
dc.identifier.hkuros305874-
dc.identifier.volume106-
dc.identifier.issue2-
dc.identifier.spage402-
dc.identifier.epage414-
dc.publisher.placeUnited States-

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