The liver is a tantalizing organ to model because of its role in drug metabolism and as a target for treatment as our understanding of nonalcoholic steatohepatitis (NASH) grows. However, in order to effectively assess the safety and efficacy of therapeutics in the context of the liver, a reliable and relevant in vitro model needs to be developed. In this blog post we describe how advanced cell culture models are being used in this space and how switching to 3D cell culture models from 2D cell culture models can actually be more inexpensive while providing a greater level of in vivo relevance.
Drug-induced-liver-injury (DILI) is the cause of many late stage drug failures and is a leading cause of drug withdrawals in the post-marketing phase. DILI can be broken down into two broad categories which are intrinsic and idiosyncratic. Intrinsic DILI is dose dependent and is reproducible in animal models. Conversely, idiosyncratic DILI is classified as not clearly related to dose, route, or duration of drug administration. Therefore, idiosyncratic DILI is definitionally poorly understood, challenging to model and the typical cause of liver related late stage drug attrition.
NASH and NAFLD are the pathologic accumulation of fibrotic tissue in the liver leading to diminished organ function and ultimately organ failure. The mechanistic causes are still being explored, but typically being overweight leads to an accumulation of lipids in the liver resulting in liver inflammation and the buildup of scar tissue. Approximately 35% of adults in the US are affected and associated costs are greater than $100 billion per year.
This finally brings us to the case for 3D cell-based liver models as an inexpensive approach for modeling DILI, NASH and NAFLD to evaluate the safety and efficacy of novel therapeutics. When seeding primary liver cells for 2D culture in a 96 well plate it takes approximately 50,000 cells per well to form an adequate monolayer. A vial of cryopreserved primary human hepatocytes come with approximately 5 million cells, so it takes one vial of cells per 96 well plate. When making spheroids it takes approximately 1,000 cells per spheroid. Therefore, one 96 well plate requires 100,000 cells, and one cryovial of cells can make 50 96 well plates of spheroids.
The consensus around 3D cell culture is that while it can be more clinically applicable when compared with 2D culture in the right situation, it is always more complex and costly to setup and run. If cells are a major expense for an experiment, like when working with primary cells, switching to 3D cell culture could be a surprising way to actually cut costs. If you are curious how to switch your cell based assay from 2D to 3D reach out to the Visikol team today.