Application of Multivariate Analysis to Optimize Function of Cultured Hepatocytes

Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. To characterize intermediary metabolism in the hepatocytes, metabolic flux analysis (MFA) was appli...

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Bibliographic Details
Published in:Biotechnology progress 2003-03, Vol.19 (2), p.580-598
Main Authors: Chan, Christina, Hwang, Daehee, Stephanopoulos, Gregory N., Yarmush, Martin L., Stephanopoulos, George
Format: Article
Language:English
Subjects:
Algorithms
Animals
Biological and medical sciences
Cell Culture Techniques - methods
Cells, Cultured
Computers
Culture Media, Conditioned - metabolism
Female
Fundamental and applied biological sciences. Psychology
Hepatocytes - metabolism
Insulin - metabolism
Models, Biological
Models, Statistical
Multienzyme Complexes - metabolism
Multivariate Analysis
Rats
Rats, Inbred Lew
Signal Transduction - physiology
Triglycerides - metabolism
Urea - metabolism
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Summary:Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. To characterize intermediary metabolism in the hepatocytes, metabolic flux analysis (MFA) was applied to elucidate the changes in intracellular pathway fluxes of primary rat hepatocytes exposed to human plasma and to provide a comprehensive snapshot of the hepatic metabolic profile. In the current study, the combination of preconditioning and plasma supplementation produced distinct metabolic states. Combining the metabolic flux distribution obtained by MFA with methodologies such as Fisher discriminant analysis (FDA) and partial least squares or projection to latent structures (PLS) provided insights into the underlying structure and causal relationship within the data. With the aid of these analyses, patterns in the cellular response of the hepatocytes that contributed to the separation of the different hepatic states were identified. Of particular interest was the recognition of distal pathways that strongly correlated with a particular hepatic function. The hepatic functions investigated were intracellular triglyceride accumulation and urea production. This study illustrates a framework for optimizing hepatic function and a possibility of identifying potential targets for improving hepatic functions.
ISSN:8756-7938
1520-6033
DOI:10.1021/bp025660h