Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation

Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and strongly correlates with the growing incidence of obesity and type II diabetes. We have developed a human-on-a-chip model composed of human hepatocytes and adipose tissue chambers capable of modeling the metabolic...

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Autores principales:	Victoria L. Slaughter, John W. Rumsey, Rachel Boone, Duaa Malik, Yunqing Cai, Narasimhan Narasimhan Sriram, Christopher J. Long, Christopher W. McAleer, Stephen Lambert, Michael L. Shuler, J. J. Hickman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3547c91f62364f5898fce5860fb718e0
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spelling	oai:doaj.org-article:3547c91f62364f5898fce5860fb718e02021-12-02T18:02:50ZValidation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation10.1038/s41598-021-92264-22045-2322https://doaj.org/article/3547c91f62364f5898fce5860fb718e02021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92264-2https://doaj.org/toc/2045-2322Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and strongly correlates with the growing incidence of obesity and type II diabetes. We have developed a human-on-a-chip model composed of human hepatocytes and adipose tissue chambers capable of modeling the metabolic factors that contribute to liver disease development and progression, and evaluation of the therapeutic metformin. This model uses a serum-free, recirculating medium tailored to represent different human metabolic conditions over a 14-day period. The system validated the indirect influence of adipocyte physiology on hepatocytes that modeled important aspects of NAFLD progression, including insulin resistant biomarkers, differential adipokine signaling in different media and increased TNF-α-induced steatosis observed only in the two-tissue model. This model provides a simple but unique platform to evaluate aspects of an individual factor’s contribution to NAFLD development and mechanisms as well as evaluate preclinical drug efficacy and reassess human dosing regimens.Victoria L. SlaughterJohn W. RumseyRachel BooneDuaa MalikYunqing CaiNarasimhan Narasimhan SriramChristopher J. LongChristopher W. McAleerStephen LambertMichael L. ShulerJ. J. HickmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Victoria L. Slaughter John W. Rumsey Rachel Boone Duaa Malik Yunqing Cai Narasimhan Narasimhan Sriram Christopher J. Long Christopher W. McAleer Stephen Lambert Michael L. Shuler J. J. Hickman Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation
description	Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and strongly correlates with the growing incidence of obesity and type II diabetes. We have developed a human-on-a-chip model composed of human hepatocytes and adipose tissue chambers capable of modeling the metabolic factors that contribute to liver disease development and progression, and evaluation of the therapeutic metformin. This model uses a serum-free, recirculating medium tailored to represent different human metabolic conditions over a 14-day period. The system validated the indirect influence of adipocyte physiology on hepatocytes that modeled important aspects of NAFLD progression, including insulin resistant biomarkers, differential adipokine signaling in different media and increased TNF-α-induced steatosis observed only in the two-tissue model. This model provides a simple but unique platform to evaluate aspects of an individual factor’s contribution to NAFLD development and mechanisms as well as evaluate preclinical drug efficacy and reassess human dosing regimens.
format	article
author	Victoria L. Slaughter John W. Rumsey Rachel Boone Duaa Malik Yunqing Cai Narasimhan Narasimhan Sriram Christopher J. Long Christopher W. McAleer Stephen Lambert Michael L. Shuler J. J. Hickman
author_facet	Victoria L. Slaughter John W. Rumsey Rachel Boone Duaa Malik Yunqing Cai Narasimhan Narasimhan Sriram Christopher J. Long Christopher W. McAleer Stephen Lambert Michael L. Shuler J. J. Hickman
author_sort	Victoria L. Slaughter
title	Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation
title_short	Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation
title_full	Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation
title_fullStr	Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation
title_full_unstemmed	Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation
title_sort	validation of an adipose-liver human-on-a-chip model of nafld for preclinical therapeutic efficacy evaluation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3547c91f62364f5898fce5860fb718e0
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Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation

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