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

  • 40 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.

LanguageEnglish (US)
Pages580-598
Number of pages19
JournalBiotechnology Progress
Volume19
Issue number2
DOIs
StatePublished - Mar 2003

Profile

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

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. 2003 ; Vol. 19, No. 2. pp. 580-598
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