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Microscale culture of human liver cells for drug development

Tissue function depends on hierarchical structures extending from single cells (∼10 μm) to functional subunits (100 μm-1 mm) that coordinate organ functions. Conventional cell culture disperses tissues into single cells while neglecting higher-order processes. The application of semiconductor-driven... Full description

Journal Title: Nature biotechnology 2008-01, Vol.26 (1), p.120-126
Main Author: Bhatia, Sangeeta N
Other Authors: Khetani, Salman R
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1087-0156
Link: https://www.ncbi.nlm.nih.gov/pubmed/18026090
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title: Microscale culture of human liver cells for drug development
format: Article
creator:
  • Bhatia, Sangeeta N
  • Khetani, Salman R
subjects:
  • Biological Assay - instrumentation
  • Biological Assay - methods
  • Biomedical research
  • Cell Culture Techniques - instrumentation
  • Cell Culture Techniques - methods
  • Cells
  • Cells, Cultured
  • Drug Design
  • Equipment Design
  • Equipment Failure Analysis
  • Flow Injection Analysis - instrumentation
  • Flow Injection Analysis - methods
  • Gene expression
  • Genetic aspects
  • Hepatocytes - cytology
  • Hepatocytes - physiology
  • Humans
  • Identification and classification
  • Liver
  • Liver cells
  • Methods
  • Microfluidic Analytical Techniques - instrumentation
  • Microfluidic Analytical Techniques - methods
  • Miniaturization
  • Pharmaceutical research
  • Pharmaceuticals
  • Phenotype
  • Semiconductors
  • Toxicity
  • Toxins
ispartof: Nature biotechnology, 2008-01, Vol.26 (1), p.120-126
description: Tissue function depends on hierarchical structures extending from single cells (∼10 μm) to functional subunits (100 μm-1 mm) that coordinate organ functions. Conventional cell culture disperses tissues into single cells while neglecting higher-order processes. The application of semiconductor-driven microtechnology in the biomedical arena now allows fabrication of microscale tissue subunits that may be functionally improved and have the advantages of miniaturization. Here we present a miniaturized, multiwell culture system for human liver cells with optimized microscale architecture that maintains phenotypic functions for several weeks. The need for such models is underscored by the high rate of pre-launch and post-market attrition of pharmaceuticals due to liver toxicity. We demonstrate utility through assessment of gene expression profiles, phase I/II metabolism, canalicular transport, secretion of liver-specific products and susceptibility to hepatotoxins. The combination of microtechnology and tissue engineering may enable development of integrated tissue models in the so-called 'human on a chip'.
language: eng
source:
identifier: ISSN: 1087-0156
fulltext: no_fulltext
issn:
  • 1087-0156
  • 1546-1696
url: Link


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descriptionTissue function depends on hierarchical structures extending from single cells (∼10 μm) to functional subunits (100 μm-1 mm) that coordinate organ functions. Conventional cell culture disperses tissues into single cells while neglecting higher-order processes. The application of semiconductor-driven microtechnology in the biomedical arena now allows fabrication of microscale tissue subunits that may be functionally improved and have the advantages of miniaturization. Here we present a miniaturized, multiwell culture system for human liver cells with optimized microscale architecture that maintains phenotypic functions for several weeks. The need for such models is underscored by the high rate of pre-launch and post-market attrition of pharmaceuticals due to liver toxicity. We demonstrate utility through assessment of gene expression profiles, phase I/II metabolism, canalicular transport, secretion of liver-specific products and susceptibility to hepatotoxins. The combination of microtechnology and tissue engineering may enable development of integrated tissue models in the so-called 'human on a chip'.
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subjectBiological Assay - instrumentation ; Biological Assay - methods ; Biomedical research ; Cell Culture Techniques - instrumentation ; Cell Culture Techniques - methods ; Cells ; Cells, Cultured ; Drug Design ; Equipment Design ; Equipment Failure Analysis ; Flow Injection Analysis - instrumentation ; Flow Injection Analysis - methods ; Gene expression ; Genetic aspects ; Hepatocytes - cytology ; Hepatocytes - physiology ; Humans ; Identification and classification ; Liver ; Liver cells ; Methods ; Microfluidic Analytical Techniques - instrumentation ; Microfluidic Analytical Techniques - methods ; Miniaturization ; Pharmaceutical research ; Pharmaceuticals ; Phenotype ; Semiconductors ; Toxicity ; Toxins
ispartofNature biotechnology, 2008-01, Vol.26 (1), p.120-126
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descriptionTissue function depends on hierarchical structures extending from single cells (∼10 μm) to functional subunits (100 μm-1 mm) that coordinate organ functions. Conventional cell culture disperses tissues into single cells while neglecting higher-order processes. The application of semiconductor-driven microtechnology in the biomedical arena now allows fabrication of microscale tissue subunits that may be functionally improved and have the advantages of miniaturization. Here we present a miniaturized, multiwell culture system for human liver cells with optimized microscale architecture that maintains phenotypic functions for several weeks. The need for such models is underscored by the high rate of pre-launch and post-market attrition of pharmaceuticals due to liver toxicity. We demonstrate utility through assessment of gene expression profiles, phase I/II metabolism, canalicular transport, secretion of liver-specific products and susceptibility to hepatotoxins. The combination of microtechnology and tissue engineering may enable development of integrated tissue models in the so-called 'human on a chip'.
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abstractTissue function depends on hierarchical structures extending from single cells (∼10 μm) to functional subunits (100 μm-1 mm) that coordinate organ functions. Conventional cell culture disperses tissues into single cells while neglecting higher-order processes. The application of semiconductor-driven microtechnology in the biomedical arena now allows fabrication of microscale tissue subunits that may be functionally improved and have the advantages of miniaturization. Here we present a miniaturized, multiwell culture system for human liver cells with optimized microscale architecture that maintains phenotypic functions for several weeks. The need for such models is underscored by the high rate of pre-launch and post-market attrition of pharmaceuticals due to liver toxicity. We demonstrate utility through assessment of gene expression profiles, phase I/II metabolism, canalicular transport, secretion of liver-specific products and susceptibility to hepatotoxins. The combination of microtechnology and tissue engineering may enable development of integrated tissue models in the so-called 'human on a chip'.
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