Cell sources forin vitrohuman liver cell culture models

Abstract

In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro. However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro. Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described.

Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent

“…PHH have long been considered the gold standard cell source to create in vitro liver models (205). When kept in suspension, gene expression patterns are well maintained and are comparable to those observed in the liver of origin (206).…”

Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models

“…Currently, the widespread used in vitro liver models have focused on culturing hepatocytes or coculturing hepatocytes with nonparenchymal cells[59b] to more closely mimic the physiology of the human liver microenvironment. The liver cell sources are animal‐derived cells and human hepatic cells (e.g., primary human liver cells, cell lines derived from hepatoma cells, and adult/embryonic/induced pluripotent stem cells). Models using whole liver and liver slices are also reported where the native liver tissue architecture and cell composition can be retained .…”

The application of in vitro models in a preclinical safety evaluation of new drug candidates

“…Wykorzystywane są także komórki macierzyste: -dojrzałe komórki macierzyste pochodzące z wątroby lub z komórek niewątrobowych, np. mezenchymalne komórki macierzyste (MSC); -pluripotencjalne komórki macierzyste, reprezentowane głównie przez ludzkie embrionalne komórki macierzyste (hESC) i indukowane przez człowieka pluripotencjalne komórki macierzyste (hiPSC), ze względu na ich zdolność do proliferacji i różnicowania w komórki hepatocytopodobne [14,15].…”

“…Jedną z wad stosowania pierwotnych hepatocytów do badań toksykologicznych jest utrata fenotypu po niedługim czasie w hodowli. Funkcje specyficzne dla wątroby, takie jak wytwarzanie albumin i ekspresja enzymów cytochromu P450, zostają utracone już w ciągu pierwszych 24-48 godzin hodowli [15,16].…”