In Vitro-Engineered Service for NASH Model

While developing various biomarkers or targets to better diagnose or treat non-alcoholic steatohepatitis (NASH), preclinical testing tools are needed for compound screening and mechanical studies. As part of our portfolio of NASH-related services, Creative Biolabs offers customized in vitro-engineered liver model services to study drugs or biomarkers for NASH treatment.

The Strategies for In Vitro NASH Model Development

More and more in vitro-engineered liver models using new cellular tools are available for NASH research. They will improve the pathophysiology of this rapidly increasing common disease and promote new strategies for its treatment. In general, although the advantages of in vitro models are evident in the molecular mechanisms involved in the analysis of liver damage, they are limited by relatively simple settings compared to more complex whole human organs. Cell culture models of NASH have been developed to reveal the molecular mechanisms involved in the onset and progression of this liver disease, and to serve as a tool to test new treatment and prevention strategies. Moreover, the inherent differences between models and experimental conditions should be properly assessed to prevent unproven and inappropriate extrapolation. With all these warnings, efforts to establish reliable in vitro models for hepatic steatosis research will greatly help limit long-term damage associated with this pandemic disease. Based on these terms, a number of different in vitro models have been established.

Strategies for in vitro NASH model development. Fig.1 Strategies forin vitro NASH model development. (Boeckmans, 2018)

Co-Culture Model

In general, primary cell cultures and immortalized cell lines are widely used to develop in vitro models for research. The interaction of two or more cells is a common phenomenon in the complex structure of liver tissue in vivo. Therefore, reproducing these settings in in vitro experiments can be a reliable model for studying cell-cell interactions in disease progression. Co-culture of two different cells is an interesting attempt to explore the important interactions. Culture of hepatocytes and hepatic stellate cells (HSCs) has shown that the differentiation of hepatocytes is improved by cell contact and soluble factors (maintaining liver-specific functions and structures).

In Vitro Microfluidic Model

Microfluidic devices are supported by live cell microscopy, high content analysis (HCA) and computational modeling, which form a powerful tool for cell analysis. They play an important role in integrating the 3D tissue engineering model into a powerful preclinical platform. The microfluidic model of human NASH develops in a sinusoidal and dynamic condition within a microfluidic device, representing a tissue-like microenvironment of hepatocyte cultures longer than conventional 2D static culture because of its quasi-3D and perfusion design. Compared to 2D static counterparts, the developed model results in a gradual and milder accumulation of intracellular triglycerides and higher hepatocyte viability, which more closely mimics the chronic conditions of steatosis observed in vivo. The technical advantages provided by the 3D microfluidic environment with hepatocyte cultures are primarily used for in vitro liver metabolism and toxicology studies.

The applications of microtechnology for liver study. Fig.2 The applications of microtechnology for liver study. (Lee, 2015)

Cell models that recapitulate the features of NASH mainly contain hepatocytes and stellate cells in co-culture or in 3D models. For NASH studies in vitro, Creative Biolabs offers models to mimic the progression of NASH in vitro based on our in vitro-engineered liver model platform. If you have any special need in in vitro preclinical model services or be interested in learning more about our preclinical model services, please feel free to contact us for more details.

References

  1. Boeckmans, J.; et al. Human-based systems: mechanistic NASH modeling just around the corner. Pharmacological research. 2018.
  2. Lee, K.H.; et al. 3D liver models on a microplatform: well-defined culture, engineering of liver tissue and liver-on-a-chip. Lab on a Chip. 2015, 15(19): 3822-3837.
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