Application of multivariate analysis to optimize function of cultured hepatocytes

Christina Chan, Daehee Hwang, Gregory N. Stephanopoulos, Martin L. Yarmush, George Stephanopoulos

    Research output: Contribution to journalArticle

    • 38 Citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)580-598
    Number of pages19
    JournalBiotechnology Progress
    Volume19
    Issue number2
    DOIs
    StatePublished - Mar 2003

    Profile

    Hepatocytes
    Multivariate Analysis
    Liver
    hepatocytes
    liver function
    Metabolic Flux Analysis
    discriminant analysis
    multivariate analysis
    least squares
    urea
    triacylglycerols
    liver
    metabolism
    rats
    methodology
    Artificial Liver
    Metabolome
    Discriminant Analysis
    Metabolic Networks and Pathways
    Least-Squares Analysis

    ASJC Scopus subject areas

    • Food Science
    • Biotechnology
    • Microbiology

    Cite this

    Chan, C., Hwang, D., Stephanopoulos, G. N., Yarmush, M. L., & Stephanopoulos, G. (2003). Application of multivariate analysis to optimize function of cultured hepatocytes. Biotechnology Progress, 19(2), 580-598. DOI: 10.1021/bp025660h

    Application of multivariate analysis to optimize function of cultured hepatocytes. / Chan, Christina; Hwang, Daehee; Stephanopoulos, Gregory N.; Yarmush, Martin L.; Stephanopoulos, George.

    In: Biotechnology Progress, Vol. 19, No. 2, 03.2003, p. 580-598.

    Research output: Contribution to journalArticle

    Chan, C, Hwang, D, Stephanopoulos, GN, Yarmush, ML & Stephanopoulos, G 2003, 'Application of multivariate analysis to optimize function of cultured hepatocytes' Biotechnology Progress, vol 19, no. 2, pp. 580-598. DOI: 10.1021/bp025660h
    Chan C, Hwang D, Stephanopoulos GN, Yarmush ML, Stephanopoulos G. Application of multivariate analysis to optimize function of cultured hepatocytes. Biotechnology Progress. 2003 Mar;19(2):580-598. Available from, DOI: 10.1021/bp025660h

    Chan, Christina; Hwang, Daehee; Stephanopoulos, Gregory N.; Yarmush, Martin L.; Stephanopoulos, George / Application of multivariate analysis to optimize function of cultured hepatocytes.

    In: Biotechnology Progress, Vol. 19, No. 2, 03.2003, p. 580-598.

    Research output: Contribution to journalArticle

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