Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells

Arterioscler Thromb Vasc Biol. 2017 Nov;37(11):1994-1999. doi: 10.1161/ATVBAHA.117.309199. Epub 2017 Aug 17.

Abstract

Inborn errors of hepatic metabolism are because of deficiencies commonly within a single enzyme as a consequence of heritable mutations in the genome. Individually such diseases are rare, but collectively they are common. Advances in genome-wide association studies and DNA sequencing have helped researchers identify the underlying genetic basis of such diseases. Unfortunately, cellular and animal models that accurately recapitulate these inborn errors of hepatic metabolism in the laboratory have been lacking. Recently, investigators have exploited molecular techniques to generate induced pluripotent stem cells from patients' somatic cells. Induced pluripotent stem cells can differentiate into a wide variety of cell types, including hepatocytes, thereby offering an innovative approach to unravel the mechanisms underlying inborn errors of hepatic metabolism. Moreover, such cell models could potentially provide a platform for the discovery of therapeutics. In this mini-review, we present a brief overview of the state-of-the-art in using pluripotent stem cells for such studies.

Keywords: embryonic stem cells; genome-wide association study; hypercholesterolemia type II; liver; mutation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Differentiation*
  • Cell Line
  • Drug Discovery / methods
  • Gene Expression Regulation, Developmental
  • Genetic Predisposition to Disease
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Hepatocytes / pathology
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism*
  • Induced Pluripotent Stem Cells / pathology
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Metabolism, Inborn Errors / drug therapy
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism*
  • Metabolism, Inborn Errors / pathology
  • Mutation*
  • Phenotype