In vitro models for MAFLD a 2024 update

In vitro models for MAFLD: a 2024 update

In vitro models for MAFLD: a 2024 update

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is the most common chronic liver disease, affecting around 25 % of the world population. It is characterized by an accumulation of fats in the liver (steatosis) that can lead to chronic fibroinflammatory liver injury and cirrhosis with liver failure at the end stages. 

Despite its high prevalence, there are no approved treatments for specifically treating MAFLD. Constant failure of potential drugs in preclinical and clinical phases reinforces the need for reliable preclinical models.  

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Preclinical models for MAFLD: where are we at?

In vitro models are a suitable alternative to animal models for studying MAFLD, providing accurate human relevance and predictivity. 

A review by Jimenez Ramos et al. indicated that 2D and 3D cultures have been extensively used in MAFLD research and in vitro modeling. After reviewing 146 papers from 2007 to 2021, 2D monocultures were the preferred platform for studying MAFLD (59.4%), followed by far for 2D co-cultures (14%), liver-on-a-chip (7.8%), spheroids (7.3%), collagen gel sandwiches (1.2%) and micropatterned cultures (0.6%). 

Nevertheless, they detected an increasing trend in the publication of 3D in vitro models, which already foresaw the explosion of technologies such as organoids or organ-on-a-chip in 2022 and 2023.

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3D in vitro models to mimic MAFLD

Although 2D models are cost-effective, easy to use, and suitable for high-throughput screening, they fail to recapitulate the disease phenotype. They lack cell-extracellular matrix interactions and rarely include non-parenchymal cells (NPCs). MAFLD is a multicellular disease involving all cell types in the human liver.

3D models offer an excellent platform for studying disease progression and drug screening due to their mimicking in vivo MAFLD conditions. 

Commonly 3D approaches used to study MAFLD include:  

    • Spheroids

Spheroids are compact, rounded spheres, typically consisting of only one cell type, usually HepG2 or primary human hepatocytes (PHH). In MAFLD modeling, the most popular method to form them is liquid overlay using ultra-low adhesive surface plates. Hepatic spheroids enable induction and research of steatosis for up to 5 weeks. PHH-based spheroids provide an ideal platform to study the impact of inter-individual variations in drug responses, the primary cause of drug withdrawal from the market. 

    • Organoids

Liver organoids are 3D structures derived from stem cells, progenitors, or differentiated cells that self-organize in a matrix-rich 3D environment to recapitulate aspects of the native tissue architecture and function. 

Murine-derived organoids have been widely used to model MAFLD phenotype, combining hepatocytes and activated stellate cells, but they can only approximate the pathophysiology of human MAFLD. Human organoids using pluripotent stem cells (PSCs) and iPSCs-derived hepatocytes, in combination with NPCs, such as stellate cells and Kupffer cells, have also been used. 

    • Organ-on-a-chip

Organ-on-a-chip enables automated control over fluid shear stress, nutrient and gas exchange, or waste removal to model the liver microenvironment, favoring reproducibility thanks to the standardized fabrication process of chips. Besides including diverse cell types, multi-organ-on-a-chip mimics the interaction between different organs involved in disease progression, such as the gut. Gut-liver-on-a-chip devices have already been developed, providing a comprehensive vision of the pathology.  

    • Precision-cut liver slices 

Precision-cut liver slices (PCLSs) consist of slicing fresh liver tissue from either explants or biopsies, thus maintaining tissue architecture and cellular organization. It presents significant limitations for studying circulating agent roles in liver disease, such as blood immune cells. In most setups, PCLSs may only be used for up to 5 days, limiting the study of slow-progressing pathologic mechanisms. 

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Level up your in vitro model with BeCytes!

No matter what your model is, our cells will suit it! 

BeCytes is dedicated to providing MAFDL hepatocytes directly from diagnosed patients to advance the development of research into this growing epidemic. Check the available lots in our inventory by selecting the cell type and adjusting the parameters. 

Our extensive portfolio also offers human primary hepatocytes, fresh or cryopreserved, and human non-parenchymal cells, including Kupffer Cellsliver endothelial cells/liver sinusoidal endothelial cells, and stellate cells. 

If you have any doubt, don’t hesitate to contact us at info@cytesbiotech.com

We are here to speed up your research!

References

Ramos MJ, Bandiera L, Menolascina F, Fallowfield JA. In vitro models for non-alcoholic fatty liver disease: Emerging platforms and their applications. iScience. 2021 Dec 4;25(1):103549. doi: 10.1016/j.isci.2021.103549

Rezvani M, Vallier L, Guillot A. Modeling Nonalcoholic Fatty Liver Disease in the Dish Using Human-Specific Platforms: Strategies and Limitations. Cell Mol Gastroenterol Hepatol. 2023;15(5):1135-1145. doi: 10.1016/j.jcmgh.2023.01.014

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