Recapitulation of metabolic defects in a model of propionic acidemia using patient-derived primary hepatocytes.

ABSTRACT:

Background

Propionic acidemia (PA) is a disorder of intermediary metabolism with defects in the alpha or beta subunits of propionyl CoA carboxylase (PCCA and PCCB respectively) enzyme. We previously described a liver culture system that uses liver-derived hemodynamic blood flow and transport parameters to restore and maintain primary human hepatocyte biology and metabolism utilizing physiologically relevant milieu concentrations.

Methods

In this study, primary hepatocytes isolated from the explanted liver of an 8-year-old PA patient were cultured in the liver system for 10 days and evaluated for retention of differentiated polarized morphology. The expression of PCCA and PCCB was assessed at a gene and protein level relative to healthy donor controls. Ammonia and urea levels

SUBMITTER: Chapman KA 

PROVIDER: S-EPMC4852394 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature