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.

HNF4alpha expression amplifies the glucocorticoid-induced conversion of a human pancreatic cell line to an hepatocyte-like cell

“…Previous experience with rat B-13 cells has demonstrated that the hepatocyte-like B-13/H cells derived therefrom show good comparability with primary rat hepatocytes with respect to several cytochrome P450s and sensitivities to drug/chemical toxicity [8][9][10][12][13][14]. Exposing HPAC cells to glucocorticoid had a variety of effects also observed when B-13 cells were treated with glucocorticoid, including an inhibition in proliferation, phenotypic changes and low level expression 7 of a variety of hepatocyte-specific transcripts (e.g.…”

“…Understanding the apparent obliviousness of B-13/H cells to their environment and applying this to stem cells may be one way to overcome the reluctance of stem cells to fully differentiate into quantitatively equivalent, stable adult hepatocytes in vitro, and prevent their de-differentiation. B-13 cells were originally derived from the rat pancreas and appear to behave as an immortal pancreatohepatobiliary progenitor cell line restricted to differentiation to B-13/H cells [11,12].…”

B-13 progenitor-derived hepatocytes (B-13/H cells) model lipid dysregulation in response to drugs and chemicals

“…The B-13 cell line – originally cloned from the rat exocrine pancreatic cancer cell line AR42J ( Mashima et al, 1996 ) – could offer a potential route to delivering a cost-effective, simple solution to the production of functional hepatocytes in vitro (for a full description of its derivation, see Probert et al, 2015 ). The B-13 cell is readily expandable in simple culture medium, does not require an extensive array of recombinant growth factors to retain its phenotype nor require sub-culture from non-progenitor cell types (such as fibroblasts) in its expansion, in contrast to pluripotent stem cells ( Probert et al, 2015 ). Furthermore, B-13 cells do not require an extensive array of recombinant growth factors and/or other signalling inhibitor treatments to direct them to become hepatocytes.…”

Transdifferentiated rat pancreatic progenitor cells (AR42J-B13/H) respond to phenobarbital in a rat hepatocyte-specific manner.

“…It was reported by Shen et al, (Shen et al 2000) that treatment of the undifferentiated B13 cell with dexamethasone for two weeks stimulated the cell to transdifferentiate into hepatocyte-like B13/H cells. The differentiated cell population display gene expression profiles similar to primary hepatocytes and can be maintained in culture for considerably longer than primary hepatocytes without de-differentiation (Probert et al 2013;Probert et al 2015), making them a useful model for the proposed treatments here.…”

“…However primary hepatocytes rapidly lose their hepatic phenotype, and so the use of alternative models such as stem-cell derived hepatocytes has become the focus of intense research (Hu and Li 2015). In the rat, it has been proposed that the pancreatic derived progenitor cell line, AR42J-B13 (B13 cells), offers a stable, cost-effective and easy model for generating hepatocyte-like cells known as AR42J-B13/H (B13/H) (Probert et al 2015). It was reported by Shen et al, (Shen et al 2000) that treatment of the undifferentiated B13 cell with dexamethasone for two weeks stimulated the cell to transdifferentiate into hepatocyte-like B13/H cells.…”