An expandable donor-free supply of functional hepatocytes for toxicology

Abstract

The B-13 cell is a readily expandable rat pancreatic acinar-like cell that differentiates on simple plastic culture substrata into replicatively-senescent hepatocyte-like (B-13/H) cells in response to glucocorticoid exposure. B-13/H cells express a variety of liver-enriched and liver-specific genes, many at levels similar to hepatocytes in vivo. Furthermore, the B-13/H phenotype is maintained for at least several weeks in vitro, in contrast to normal hepatocytes which rapidly de-differentiate under the same simple – or even under more complex – culture conditions. The origin of the B-13 cell line and the current state of knowledge regarding differentiation to B-13/H cells are presented, followed by a review of recent advances in the use of B-13/H cells in a variety of toxicity endpoints. B-13 cells therefore offer Toxicologists a cost-effective and easy to use system to study a range of toxicologically-related questions. Dissecting the mechanism(s) regulating the formation of B-13/H cell may also increase the likelihood of engineering a human equivalent, providing Toxicologists with an expandable donor-free supply of functional rat and human hepatocytes, invaluable additions to the tool kit of in vitro toxicity tests.