Resulting from a research collaboration between NFRG* and the Pharmaceutical company Abbvie, a new poster has been presented by Hannah Paish at 2018 edition of the Institute of Sciences and Technology (IST) Technical Conference, entitled:

A novel bioreactor technology for modelling fibrosis in human and rodent precision-cut liver slices

Abstract

Precision-cut liver slices (PCLS) retain the structure and cellular composition of the native liver and represent an improved system to study liver fibrosis compared to two-dimensional mono or co-cultures.

The objective of this study was to develop a bioreactor system to increase the healthy lifespan ofPCLS and model fibrogenesis.

PCLS were generated from normal rat or human liver and cultured in our patented bioreactor. PCLS function was quantified by albumin ELISA. Fibrosis was induced in PCLS by transforming growth factor beta1 (TGFβ1) and Platelet-derived growth factor (PDGFββ) stimulation+/-therapy. Fibrosis was assessed by fibrogenic gene expression, Picrosirius Red (collagen) and αSmooth Muscle Actin (activated hepatic stellate cells) staining.

Bioreactor cultured PCLS are viable, maintaining tissue structure and stable albumin secretion for up to 4 days under normoxic culture conditions. Conversely, standard static transwell cultured PCLS rapidly deteriorate and albumin secretion is significantly impaired by 48hours.

TGFβ1/PDGFββ stimulation of rat or human PCLS induced fibrogenic gene expression, activation of hepatic myofibroblasts and histological fibrosis. Alk5 inhibitor therapy limited fibrogenesis in TGFβ1/PDGFββ stimulated rat and human PCLS.