Gotta Love a “GOOD” model! For the liver that is!

Researchers are constantly searching for methods to generate models for testing hypotheses within the context of biological relevance. Not only is it important to generate models that are fully functional to test an hypothesis, but these models must mimic that biological system of interest as seen within its natural context. Scientists at the University of Leipzig in Germany are lending their expertise in this emerging area with particular focus on the liver. The liver plays a variety of very pivotal roles in the human body, such as detoxifying drugs and other substances that we ingest,  protein synthesis and fat metabolism.

Primary hepatocytes (liver cells) present an appropriate model for the validation of a system for toxicological studies of new drugs and chemicals that may be used in the pharmaceutical/cosmetics industries and biologically relevant models are needed to test the affects of these chemicals within a biological context. However, there are no models currently available to do this.

Dr. Peggy Stock and her colleagues at the University of Leipzig in Germany are conducting research in generating appropriate models for liver toxicity studies. In preliminary studies presented at the 2012 Experimental Biology Conference in San Diego, California, this group presented data analysing the applicability of using 3D versus 2D collagen-coated silicone scaffolds for models of human liver. This group utilized rat hepatocytes (rat liver cells) as a cellular model for human liver, since rat liver cell processes mimic that of humans to a high degree.

Primary rat hepatocytes were cultured (grown) for 72h on a 3D structure and was compared with 2D culture on conventional cell culturing methods utilizing cell culture dishes. Cell counts and the growth patterns of these cells on silicone and the urea production rate were also determined as urea production takes place in the liver and it can serve as a marker of liver health and function.

Based on identical initial cell counts the growth rate was about 42% higher in 3D culture as compared to 2D. In addition, cells attached to the scaffold and formed clusters and organ-like structures that are native to the liver. The 3D culture on the silicone scaffold displayed no significant signs of toxicity after 3 days of cell culture. The urea production rate, which is a marker of liver health and function, was significantly higher in the 3D vs 2D cell culturing system.

Results from these studies demonstrate the appropriateness of using 3D models for the culture of primary rat hepatocytes. Thus, revealing that these 3D scaffolds may be utilized as an important tool for the development of 3D liver models for understanding and examining liver function within a laboratory setting.

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