{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ronaldson-Bouchard K"],"funding":["NIBIB NIH HHS","NCATS NIH HHS","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS","U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute","NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health","U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering","National Science Foundation"],"pagination":["351-371"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9250010"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(4)"],"pubmed_abstract":["Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, liver, bone and skin tissue niches are linked by recirculating vascular flow to allow for the recapitulation of interdependent organ functions. Each tissue is cultured in its own optimized environment and is separated from the common vascular flow by a selectively permeable endothelial barrier. The interlinked tissues maintained their molecular, structural and functional phenotypes over 4 weeks of culture, recapitulated the pharmacokinetic and pharmacodynamic profiles of doxorubicin in humans, allowed for the identification of early miRNA biomarkers of cardiotoxicity, and increased the predictive values of clinically observed miRNA responses relative to tissues cultured in isolation and to fluidically interlinked tissues in the absence of endothelial barriers. Vascularly linked and phenotypically stable matured human tissues may facilitate the clinical applicability of tissue chips."],"journal":["Nature biomedical engineering"],"pubmed_title":["A multi-organ chip with matured tissue niches linked by vascular flow."],"pmcid":["PMC9250010"],"funding_grant_id":["R35 CA197745","P41 EB027062","UL1 TR001873","S10 OD012351","OD012351, S10 OD021764","DGE1644869","CA197745S10","P30 CA013696","NSF16478","CA249799","P41 EB002520","UG3 EB025765","R01 CA249799","UG3EB025765","S10 OD021764"],"pubmed_authors":["Guo Z","Jackow J","Teles D","Tamargo M","Zhao Y","Soni RK","Lee BM","Summers M","Vunjak-Novakovic G","Yeager K","Chen CS","Sonar S","Stylianos S","Abaci EH","Halligan SP","Tavakol DN","Tagore S","Przekwas A","Chramiec A","Shih J","Califano A","Pappalardo A","German C","Ronaldson-Bouchard K","Hirschi KK","Christiano AM"],"additional_accession":[]},"is_claimable":false,"name":"A multi-organ chip with matured tissue niches linked by vascular flow.","description":"Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, liver, bone and skin tissue niches are linked by recirculating vascular flow to allow for the recapitulation of interdependent organ functions. Each tissue is cultured in its own optimized environment and is separated from the common vascular flow by a selectively permeable endothelial barrier. The interlinked tissues maintained their molecular, structural and functional phenotypes over 4 weeks of culture, recapitulated the pharmacokinetic and pharmacodynamic profiles of doxorubicin in humans, allowed for the identification of early miRNA biomarkers of cardiotoxicity, and increased the predictive values of clinically observed miRNA responses relative to tissues cultured in isolation and to fluidically interlinked tissues in the absence of endothelial barriers. Vascularly linked and phenotypically stable matured human tissues may facilitate the clinical applicability of tissue chips.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-06-04T04:40:10.098Z","creation":"2025-04-06T13:27:59.406Z"},"accession":"S-EPMC9250010","cross_references":{"pubmed":["35478225"],"doi":["10.1038/s41551-022-00882-6"]}}