TY - JOUR
KW - Heart
KW - Liver
KW - MicroRNAs
KW - Skin
AU - Kacey Ronaldson-Bouchard
AU - Diogo Teles
AU - Keith Yeager
AU - Daniel Naveed Tavakol
AU - Yimu Zhao
AU - Alan Chramiec
AU - Somnath Tagore
AU - Max Summers
AU - Sophia Stylianos
AU - Manuel Tamargo
AU - Busub Marcus Lee
AU - Susan P. Halligan
AU - Erbil Hasan Abaci
AU - Zongyou Guo
AU - Joanna Jacków
AU - Alberto Pappalardo
AU - Jerry Shih
AU - Rajesh K. Soni
AU - Shivam Sonar
AU - Carrie German
AU - Angela M. Christiano
AU - Andrea Califano
AU - Karen K. Hirschi
AU - Christopher S. Chen
AU - Andrzej Przekwas
AU - Gordana Vunjak-Novakovic
AB - 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.
BT - Nature Biomedical Engineering
DA - 2022-04
DO - 10.1038/s41551-022-00882-6
IS - 4
LA - eng
N2 - 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.
PY - 2022
SP - 351
EP - 371
T2 - Nature Biomedical Engineering
TI - A multi-organ chip with matured tissue niches linked by vascular flow
VL - 6
SN - 2157-846X
ER -