作者
Kacey Ronaldson-Bouchard,Diogo Teles,Keith Yeager,Daniel Naveed Tavakol,Yong Zhao,Alan Chramiec,Somnath Tagore,Max Summers,Sophia Stylianos,Manuel A. Tamargo,Busub Marcus Lee,Susan P. Halligan,Erbil Hasan Abaci,Zongyou Guo,J. Jacków,Alberto Pappalardo,Jerry J. Shih,Rajesh Kumar Soni,Shivam Sonar,Carrie German,Angela M. Christiano,Andrea Califano,Karen K. Hirschi,Christopher Chen,Andrzej Przekwas,Gordana Vunjak‐Novakovic
摘要
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.