期刊
NATURE BIOMEDICAL ENGINEERING
卷 6, 期 4, 页码 351-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41551-022-00882-6
关键词
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资金
- NIH [UG3 EB025765, P41 EB027062, R01 CA249799, R35 CA197745, S10 OD012351, S10 OD021764, UL1 TR001873, P30 CA013696]
- NSF (Engineering Reseach Center) [EEC-1647837]
- F.C.T. [PD/BD/105819/2014]
- NSF [DGE1644869]
- Fundação para a Ciência e a Tecnologia [PD/BD/105819/2014] Funding Source: FCT
This study reports the development and application of a tissue-chip system where matured human heart, liver, bone, and skin tissue niches are interconnected by recirculating vascular flow, allowing for the replication of interdependent organ functions and potentially enhancing clinical applicability.
Tissue chips with matured human heart, liver, bone and skin tissue niches linked by recirculating vascular flow recapitulate interdependent functions of these organs. 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.
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