A considerable roadblock in the successful triaging of new therapeutics for liver and metabolic related diseases is the reliability and effectiveness of pre-clinical disease models.
Methods employing animal models may have limited success in replicating liver diseases, primarily because of species-specific differences, furthermore, the utilisation of animal models to simulate liver disease phenotypes frequently leads to limited success.
Primary hepatocytes represent the gold standard in vitro cell model for functionality. However, when isolated from liver tissue, primary cells maintain expression of key proteins for only a short period. Extending culture of primary hepatocytes beyond 24 hours may result in rapid dedifferentiation, characterised by loss of function and apoptosis.
Initial screening of treatments may utilise the highly proliferative Chinese Hamster Ovarian (CHO) or Human Embryonic Kidney (HEK) cell lines with the liver protein(s) of interest exogenously expressed. This system allows researchers to investigate the effect of the treatment on the target protein, but the cellular environment bears little resemblance to that of the human liver, an impediment to reliable compound triaging.
Hepatocellular carcinoma-derived cell lines, such as HepG2s, are less proliferative than CHO or HEK cells but remain readily expandable and retain aspects of hepatocyte function. However, hepatoma lines may lack the key proteins essential for modeling. Also, stable cell lines derived from cancers represent a single and karyotypically abnormal genotype.
An ideal model for the study of liver disease would combine the expansion capacity and phenotypic stability of hepatoma cell lines with the functionality and normal karyotype of primary can fulfil this role.
In this webinar you will discover how iPSC derived cells can be used to advance the efficiency and efficacy of disease modeling.