Development Services of NASH In Vitro Tissue Engineering Model

The progressive disease spectrum of non-alcoholic fatty liver disease (including nonalcoholic steatohepatitis (NASH)) is a rapidly emerging public health crisis with no approved treatment. The diversity of the therapies being developed highlights the lack of consensus around the most effective targets, emphasizing the need for better translatable preclinical models to study complex progressive diseases and effective therapies. Creative Biolabs has developed the unique in vitro preclinical models that accurately mimic the etiology of the disease in humans and are of great value for target identification, efficacy testing and the establishment of transforming biomarkers.

Background

The need for effective and safe treatment of human diseases stimulates the development of NASH's in vitro and animal models to better elucidate disease pathogenesis, identify potential therapeutic targets and test the therapeutic potential of single drugs or combination of drugs prior to human studies. Whereas, the difficulty of replicating complex human biology in preclinical studies may make drug development a challenging process. Compounds that appear to be effective even when tested in cell cultures and animal models often fail in humans. To improve this situation, we are working to create new in vitro models that accurately replicate human biology.

Engineering In Vitro Models of NASH

Primary cell cultures, immortalized cell lines, liver sections, and perfused liver are mature models for research work. In addition, other cell lines have been developed to help understand biological mechanisms in liver diseases, such as sinusoidal endothelial cells and Kupffer cells. Hepatic stellate cells (HSC) are the main contributor to liver fibrosis by producing excessive extracellular matrix (ECM), which can help to identify new therapies that may alter the natural history of all chronic liver diseases.

In order to translate the results of basic cell research into clinical applications, cell-based models need to recapitulate three-dimensional (3D) tissue and multicellular complexity of organs except for adapting to experimental interventions in the system. Techniques for in vitro-engineered liver model such as co-culture and microfluidics have been widely used. As a traditional technique for in vitro model culture, one of the major drawbacks of using 2D cultures to simulate living systems is the inaccurate reflection of the physiological means of applying and removing modulators, nutrients, oxygen, and metabolites. Therefore, the development of well-defined 3D multicellular organoid cultures in vitro models that mimic the in vivo ECM structures has demonstrated the importance of cell matrix biomechanics, the complex interactions between HSCs and hepatocytes and other non-parenchymal cells, which can improve and promote liver cell specific functions.

Fig.1 Schematic of different systems for culturing HSCs in vitro. (Mazza, 2017)

Based on our NASH drug discovery and antibody engineering platforms, Creative Biolabs applies our models to support preclinical R&D for NASH with features and studies to investigate including:

• Tailor-made experimental set-ups
• One-stop shop for translational research; PK/PD; toxicology
• High safety and efficiency
• Best after-sale service

If you have any special needs in NASH preclinical model services or be interested in learning more about Creative Biolabs’ NASH services, please feel free to contact us for more details.

Reference

1. Mazza, G.; et al. Engineering in vitro models of hepatofibrogenesis. Advanced drug delivery reviews. 2017, 121: 147-157.