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A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days

Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has been only limited suc...

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Autores principales: Ruoß, Marc, Häussling, Victor, Schügner, Frank, Olde Damink, Leon H. H., Lee, Serene M. L., Ge, Liming, Ehnert, Sabrina, Nussler, Andreas K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316810/
https://www.ncbi.nlm.nih.gov/pubmed/30332824
http://dx.doi.org/10.3390/bioengineering5040086
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author Ruoß, Marc
Häussling, Victor
Schügner, Frank
Olde Damink, Leon H. H.
Lee, Serene M. L.
Ge, Liming
Ehnert, Sabrina
Nussler, Andreas K.
author_facet Ruoß, Marc
Häussling, Victor
Schügner, Frank
Olde Damink, Leon H. H.
Lee, Serene M. L.
Ge, Liming
Ehnert, Sabrina
Nussler, Andreas K.
author_sort Ruoß, Marc
collection PubMed
description Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has been only limited success to allow the transport of freshly isolated hepatocytes without massive loss of function or their cultivation for a long time. Since it is well accepted that the cultivation of hepatocytes in 3D is related to an improved function, we here tested the Optimaix-3D Scaffold from Matricel for the transport and cultivation of hepatocytes. After characterization of the scaffold, we shipped cells on the scaffold and/or cultivated them over 10 days. With the evaluation of hepatocyte functions such as urea production, albumin synthesis, and CYP activity, we showed that the metabolic activity of the cells on the scaffold remained nearly constant over the culture time whereas a significant decrease in metabolic activity occurred in 2D cultures. In addition, we demonstrated that significantly fewer cells were lost during transport. In summary, the collagen-based scaffold allows the transport and cultivation of hepatocytes without loss of function over 10 days.
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spelling pubmed-63168102019-01-10 A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days Ruoß, Marc Häussling, Victor Schügner, Frank Olde Damink, Leon H. H. Lee, Serene M. L. Ge, Liming Ehnert, Sabrina Nussler, Andreas K. Bioengineering (Basel) Article Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has been only limited success to allow the transport of freshly isolated hepatocytes without massive loss of function or their cultivation for a long time. Since it is well accepted that the cultivation of hepatocytes in 3D is related to an improved function, we here tested the Optimaix-3D Scaffold from Matricel for the transport and cultivation of hepatocytes. After characterization of the scaffold, we shipped cells on the scaffold and/or cultivated them over 10 days. With the evaluation of hepatocyte functions such as urea production, albumin synthesis, and CYP activity, we showed that the metabolic activity of the cells on the scaffold remained nearly constant over the culture time whereas a significant decrease in metabolic activity occurred in 2D cultures. In addition, we demonstrated that significantly fewer cells were lost during transport. In summary, the collagen-based scaffold allows the transport and cultivation of hepatocytes without loss of function over 10 days. MDPI 2018-10-16 /pmc/articles/PMC6316810/ /pubmed/30332824 http://dx.doi.org/10.3390/bioengineering5040086 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ruoß, Marc
Häussling, Victor
Schügner, Frank
Olde Damink, Leon H. H.
Lee, Serene M. L.
Ge, Liming
Ehnert, Sabrina
Nussler, Andreas K.
A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days
title A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days
title_full A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days
title_fullStr A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days
title_full_unstemmed A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days
title_short A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days
title_sort standardized collagen-based scaffold improves human hepatocyte shipment and allows metabolic studies over 10 days
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316810/
https://www.ncbi.nlm.nih.gov/pubmed/30332824
http://dx.doi.org/10.3390/bioengineering5040086
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