Conditions for maintenance of hepatocyte differentiation and function in 3D cultures

Summary: Spheroid cultures of primary human hepatocytes (PHH) are used in studies of hepatic drug metabolism and toxicity. The cultures are maintained under different conditions, with possible confounding results. We performed an in-depth analysis of the influence of various culture conditions to fi...

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Autores principales:	Niklas Handin, Evgeniya Mickols, Magnus Ölander, Jakob Rudfeldt, Kristin Blom, Frida Nyberg, Wojciech Senkowski, Jozef Urdzik, Varun Maturi, Mårten Fryknäs, Per Artursson
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Proteomics Methodology in biological sciences Science Q
Acceso en línea:	https://doaj.org/article/6809c7fc5e7b425199479cb1e3e85b46
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spelling	oai:doaj.org-article:6809c7fc5e7b425199479cb1e3e85b462021-11-20T05:08:40ZConditions for maintenance of hepatocyte differentiation and function in 3D cultures2589-004210.1016/j.isci.2021.103235https://doaj.org/article/6809c7fc5e7b425199479cb1e3e85b462021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012037https://doaj.org/toc/2589-0042Summary: Spheroid cultures of primary human hepatocytes (PHH) are used in studies of hepatic drug metabolism and toxicity. The cultures are maintained under different conditions, with possible confounding results. We performed an in-depth analysis of the influence of various culture conditions to find the optimal conditions for the maintenance of an in vivo like phenotype. The formation, protein expression, and function of PHH spheroids were followed for three weeks in a high-throughput 384-well format. Medium composition affected spheroid histology, global proteome profile, drug metabolism and drug-induced toxicity. No epithelial-mesenchymal transition was observed. Media with fasting glucose and insulin levels gave spheroids with phenotypes closest to normal PHH. The most expensive medium resulted in PHH features most divergent from that of native PHH. Our results provide a protocol for culture of healthy PHH with maintained function - a prerequisite for studies of hepatocyte homeostasis and more reproducible hepatocyte research.Niklas HandinEvgeniya MickolsMagnus ÖlanderJakob RudfeldtKristin BlomFrida NybergWojciech SenkowskiJozef UrdzikVarun MaturiMårten FryknäsPer ArturssonElsevierarticleBiological sciencesProteomicsMethodology in biological sciencesScienceQENiScience, Vol 24, Iss 11, Pp 103235- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Proteomics Methodology in biological sciences Science Q
spellingShingle	Biological sciences Proteomics Methodology in biological sciences Science Q Niklas Handin Evgeniya Mickols Magnus Ölander Jakob Rudfeldt Kristin Blom Frida Nyberg Wojciech Senkowski Jozef Urdzik Varun Maturi Mårten Fryknäs Per Artursson Conditions for maintenance of hepatocyte differentiation and function in 3D cultures
description	Summary: Spheroid cultures of primary human hepatocytes (PHH) are used in studies of hepatic drug metabolism and toxicity. The cultures are maintained under different conditions, with possible confounding results. We performed an in-depth analysis of the influence of various culture conditions to find the optimal conditions for the maintenance of an in vivo like phenotype. The formation, protein expression, and function of PHH spheroids were followed for three weeks in a high-throughput 384-well format. Medium composition affected spheroid histology, global proteome profile, drug metabolism and drug-induced toxicity. No epithelial-mesenchymal transition was observed. Media with fasting glucose and insulin levels gave spheroids with phenotypes closest to normal PHH. The most expensive medium resulted in PHH features most divergent from that of native PHH. Our results provide a protocol for culture of healthy PHH with maintained function - a prerequisite for studies of hepatocyte homeostasis and more reproducible hepatocyte research.
format	article
author	Niklas Handin Evgeniya Mickols Magnus Ölander Jakob Rudfeldt Kristin Blom Frida Nyberg Wojciech Senkowski Jozef Urdzik Varun Maturi Mårten Fryknäs Per Artursson
author_facet	Niklas Handin Evgeniya Mickols Magnus Ölander Jakob Rudfeldt Kristin Blom Frida Nyberg Wojciech Senkowski Jozef Urdzik Varun Maturi Mårten Fryknäs Per Artursson
author_sort	Niklas Handin
title	Conditions for maintenance of hepatocyte differentiation and function in 3D cultures
title_short	Conditions for maintenance of hepatocyte differentiation and function in 3D cultures
title_full	Conditions for maintenance of hepatocyte differentiation and function in 3D cultures
title_fullStr	Conditions for maintenance of hepatocyte differentiation and function in 3D cultures
title_full_unstemmed	Conditions for maintenance of hepatocyte differentiation and function in 3D cultures
title_sort	conditions for maintenance of hepatocyte differentiation and function in 3d cultures
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/6809c7fc5e7b425199479cb1e3e85b46
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Conditions for maintenance of hepatocyte differentiation and function in 3D cultures

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