ArticleMolecular genetics and metabolism2016
Recapitulation of metabolic defects in a model of propionic acidemia using patient-derived primary hepatocytes.
Article in Molecular genetics and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Integrative genetic and liver transcriptomic analyses identify TRIB1AL as a target for steatotic liver disease.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Human cardiovascular disease model predicts xanthine oxidase inhibitor cardiovascular risk.PloS one · 2023Trial
- Loss of Propionyl-CoA Carboxylase Reprograms Hepatic Metabolism by Suppressing Mitochondrial Pyruvate Carboxylation and Fatty Acid Oxidation.bioRxiv : the preprint server for biology · 2026Article
- Propionic acid induces alterations in mitochondrial morphology and dynamics in SH-SY5Y cells.Scientific reports · 2023Article
- Genomic and biochemical analysis of repeatedly observed variants in DBT in individuals with maple syrup urine disease of Central American ancestry.American journal of medical genetics. Part A · 2022Article
- A novel small molecule approach for the treatment of propionic and methylmalonic acidemias.Molecular genetics and metabolism · 2021Article
- Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response.Scientific reports · 2021Article
- Generation of isogenic Propionyl-CoA carboxylase beta subunit (PCCB) deficient induced pluripotent stem cell lines.Stem cell research · 2020Article
- Biochemical and anaplerotic applications of in vitro models of propionic acidemia and methylmalonic acidemia using patient-derived primary hepatocytes.Molecular genetics and metabolism · 2020Article
- Translating scientific discovery: the need for preclinical models of nonalcoholic steatohepatitis.Hepatology international · 2018Review
- Propionyl-CoA carboxylase - A review.Molecular genetics and metabolism · 2017Review
- Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to disorders of propionyl-CoA metabolism.American journal of physiology. Endocrinology and metabolism · 2017Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPropionic 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.
methodsIn 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 were measured in the presence and absence of amino acid supplements to assess the metabolic consequences of branched-chain amino acid metabolism in this disease.
resultsPrimary hepatocytes from the PA patient maintained a differentiated polarized morphology (peripheral actin staining) over 10 days of culture in the system. We noted lower levels of PCCA and PCCB relative to normal healthy controls at the mRNA and protein level. Supplementation of branched-chain amino acids, isoleucine (5mM) and valine (5mM) in the medium, resulted in increased ammonia and decreased urea in the PA patient hepatocyte system, but no such response was seen in healthy hepatocytes or patient-derived fibroblasts.
conclusionsWe demonstrate for the first time the successful culture of PA patient-derived primary hepatocytes in a differentiated state, that stably retain the PCCA and PCCB enzyme defects at a gene and protein level. Phenotypic response of the system to an increased load of branched-chain amino acids, not possible with fibroblasts, underscores the utility of this system in the better understanding of the molecular pathophysiology of PA and examining the effectiveness of potential therapeutic agents in the most relevant tissue.
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