Generation of Hepatobiliary Cell Lineages from Human Induced Pluripotent Stem Cells: Applications in Disease Modeling and Drug Screening

Abstract

The possibility to reproduce key tissue functions in vitro from induced pluripotent stem cells (iPSCs) is offering an incredible opportunity to gain better insight into biological mechanisms underlying development and disease, and a tool for the rapid screening of drug candidates. This review attempts to summarize recent strategies for specification of iPSCs towards hepatobiliary lineages —hepatocytes and cholangiocytes— and their use as platforms for disease modeling and drug testing. The application of different tissue-engineering methods to promote accurate and reliable readouts is discussed. Space is given to open questions, including to what extent these novel systems can be informative. Potential pathways for improvement are finally suggested.

Novel half Salphen cobalt(iii) complexes: synthesis, DNA binding and anticancer studies

“…58 Cells cultured in a 3D support closely mimic the spatial arrangements found in the native physiological environment, leading to more reliable results that resemble in vivo biological responses. 59 Thus, we designed a series of biological assays based on 3D cell cultures of SW-1353 cells, a cell line isolated from human chondrosarcoma. To optimize the experimental conditions and identify concentrations that significantly reduce cellular population, a preliminary 2D cell viability assay based on CCK8 was performed (see the Materials and methods section for details).…”

“…58 Cells cultured in a 3D support closely mimic the spatial arrangements found in the native physiological environment, leading to more reliable results that resemble in vivo biological responses. 59…”

Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy

“…Developing more effective and repeatable procedures to generate liver organoids that can be utilized for drug screening has attracted increasing attention ever since the first reports of creating hepatocyte-like cells from iPSCs [ 126 , 127 , 128 , 129 ].…”

Hepatic Polarized Differentiation Promoted the Maturity and Liver Function of Human Embryonic Stem Cell-Derived Hepatocytes via Activating Hippo and AMPK Signaling Pathways

“…During the practice of liver cell therapies, researchers were eager to obtain fully functional human hepatocytes to achieve the desired therapeutic effect. In addition, the studies associated with human liver physiology, pathology and toxicology also need functional human hepatocytes to establish in vitro models [ 3 , 4 ]. It is no doubt that primary human hepatocytes (PHHs) remain the gold standard for these research fields mentioned above.…”