Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells

Abstract

Inborn errors of hepatic metabolism are due to 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 (GWAS) 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 (iPSCs) from patients’ somatic cells. iPSCs 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.

Modeling Alzheimer’s disease with iPSC-derived brain cells

“…Since the first publication describing how to generate iPSCs from human somatic cells in 2007, there has followed an explosion of methods to direct differentiation into the varied cell types of the body, including brain cells [48][49][50][51][52]. Methods of inducing neural progenitor cells (NPCs), numerous neuron subtypes, as well as astrocytes, microglia, oligodendrocytes, endothelial cells, and pericytes have all been established (Fig.…”

Stem Cell Therapies in Alzheimer’s Disease: Applications for Disease Modeling

“…The next year, this technology was applied to human somatic cells to generate iPSCs successfully (Takahashi et al, 2007). Since then, considerable efforts have followed to optimize this technology and reprogram cells by newly defined or fewer factors and more efficient delivery systems (Chuah and Zink, 2017;Di Lullo and Kriegstein, 2017;Pournasr and Duncan, 2017;Devalla and Passier, 2018). Lineage specifiers involved in the ectodermal specification and mesendodermal specification can synergistically induce pluripotency without Oct4 and Sox2 (Aoi, 2008;Nakagawa et al, 2008;Chia et al, 2010;Buganim and Jaenisch, 2012).…”

Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview

“…Hepatocytes-like cells derived from subsequent differentiation of iPSCs using a cocktail of growth factors and specific matrices is another alternative technique to obtain hepatocytes in vitro [24,25,62]. One disadvantage is that iPSC-derived hepatic cells are phenotypically more similar to fetal hepatocytes than to the freshly isolated counterpart [63].…”