Document Detail

Engineered three-dimensional liver mimics recapitulate critical rat-specific bile acid pathways.
MedLine Citation:
PMID:  20929286     Owner:  NLM     Status:  MEDLINE    
A critical hepatic function is the maintenance of optimal bile acid (BA) compositions to achieve cholesterol homeostasis. BAs are rarely quantified to assess hepatic phenotype in vitro since existing analytical techniques have inadequate resolution. We report a detailed investigation into the biosynthesis and homeostasis of eight primary rat BAs in conventional in vitro hepatocyte cultures and in an engineered liver mimic. The three-dimensional (3D) liver mimic was assembled with layers of primary rat hepatocytes and liver sinusoidal endothelial cells. A high-pressure liquid chromatography and mass spectrometry technique was developed with a detection limit of 1 ng/mL for each BA, which is significantly lower than previous approaches. Over a 2-week culture, only 3D liver mimics exhibited the ratio of conjugated cholic acid to chenodeoxycholic acid that has been observed in vivo. This ratio, an important marker of BA homeostasis, was significantly higher in stable collagen sandwich cultures indicating significant deviation from physiological behavior. The biosynthesis of tauro-β-muricholic acid, a key primary rat BA, doubled only in the engineered liver mimics while decreasing in the other systems. These trends demonstrate that the 3D liver mimics provide a unique platform to study hepatic metabolism.
Christopher J Detzel; Yeonhee Kim; Padmavathy Rajagopalan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-19
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  17     ISSN:  1937-335X     ISO Abbreviation:  Tissue Eng Part A     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-28     Completed Date:  2011-06-02     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  677-89     Citation Subset:  IM    
Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
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MeSH Terms
Bile Acids and Salts / chemistry,  metabolism*
Cells, Cultured
Chenodeoxycholic Acid / chemistry,  metabolism
Chromatography, High Pressure Liquid
Cytochrome P-450 Enzyme System / metabolism
Endothelial Cells / cytology,  metabolism
Glycine / metabolism
Hepatocytes / cytology,  metabolism
Liver / cytology,  physiology*
Mass Spectrometry
Metabolic Networks and Pathways*
Rats, Inbred Lew
Species Specificity
Taurine / metabolism
Tissue Engineering / methods*
Grant Support
Reg. No./Substance:
0/Bile Acids and Salts; 107-35-7/Taurine; 474-25-9/Chenodeoxycholic Acid; 56-40-6/Glycine; 9035-51-2/Cytochrome P-450 Enzyme System

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