NASH Preclinical Model Development Service

Creative Biolabs has developed unique in vivo and in vitro preclinical models that accurately mimic the etiology of NASH in humans and are of great value for target identification, efficacy testing and the establishment of translational biomarkers

Importance of Preclinical Models

With the aging population and increased duration of exposure to the non-alcoholic steatohepatitis (NASH), it is particularly noteworthy that the prevalence of cirrhosis and end-stage liver disease is likely to increase unless public health measures are taken. This underscores the importance of development pathways to accelerate the development of NASH prevention and treatment strategies. The main obstacle to the development of NASH therapeutics is the lack of preclinical disease models that have been properly validated to represent the biology and outcomes of human disease. Therefore, the need for effective and safe treatment 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 a single drug or combination of drugs prior to human studies. Here, we will focus on preclinical models of NASH, with particular attention to its translatability to human diseases.

In Vitro Tissue Engineering Models

In vitro models of NASH range from simple cell culture systems exposed to various lipids and cytokines to more complex models based on 3D multicellular organoid culture, with or without perfusion of simulated sinusoidal blood flow. Most importantly, since many hepatocytes are involved in NAFLD/NASH, the ideal in vitro model will include all relevant hepatocytes. A variety of methods, including layered co-culture, spheroids, micropatterned surfaces, human precision cut sections, and bioprinting, have been used to develop such 3D cultures to replicate the structure of the intact liver. Based on our experience, we are currently developing and commercializing liver disease platform technology specifically for the replication of NAFLD, including steatosis, fibrosis, and NASH. These disease platforms contain key aspects of human biology and disease and have applications in the areas of drug discovery and safety.

In Vivo Rat and Mouse Models

Animals have been used to study human conditions for decades. However, rodents (especially mice) are preferred in order to mimic human diseases. These smaller species are often used for a variety of reasons, including the lower costs, the shorter lifespans required for chronic diseases, and the fewer regulations than non-human primates. The ideal characteristics of the NASH animal models depend on what it will be used for. If the goal is to increase the potential for the use of drugs to improve animal NASH in human diseases, then the model studied must mimic human disease as much as possible. Animal models of NASH can be broadly classified into dietary induction, genetic or a combination of multiple interventions.

The substrate overload lipotoxic liver injury model illustrates the pathogenesis of NASH and targets of therapy. Fig.1 Pathophysiological characteristics of a good animal model to study human NAFLD and NASH. (Kohli, 2011)

With years of experience in the industry of preclinical models and excellent professional skills, Creative Biolabs is proud to help you identify the most appropriate models for your NASH research. And you can also explore our extensive and broad-based library of models to find the one you need. For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Kohli, R.; Feldstein, A.E. NASH animal models: are we there yet? Journal of hepatology. 2011, 55(4): 941-943.
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