Efforts to develop more sophisticated three-dimensional cell models have been a priority for many researchers, particularly because such models offer a number of advantages over traditional two-dimensional monolayer cell models and animal models. In vivo, different cell types interact with each other and with surrounding proteins and carbohydrates. The goal of three-dimensional cell culture models is to better mimic these interactions to create more human- and physiologically-relevant tools.
A recent article in Drug Discovery World highlighted the advantages of using three-dimensional microtissues in toxicology research. Microtissues are multicellular aggregates of cells that are engineered to mimic the smallest functional unit of tissues and organs. Different microtissue models of the liver, heart and kidney already exist and are proving to be powerful research tools in the area of in vitro toxicology.
Liver microtissues can be cultured for longer stretches of time compared to standard 2-D cultures. This allows them to be used in long-term toxicity experiments that more accurately mimic repeated dose toxicity tests performed in vivo. The article notes that these models show enhanced sensitivity in detecting toxicity and are able to predict liver toxicity “with improved in vivo relevance.”
Cardiovascular toxicity is one of the main reasons drugs fail during development, raising the concern that current pre-clinical models lack in vivo relevance. Therefore, the need to develop improved in vitro cardiotoxicity models is essential. A number of heart microtissues under development as cardiac toxicity assessment tools include critical features absent from 2-D cultures, and as a result, are better able to predict cardiotoxicity of drugs.
Drug-induced kidney toxicity is another major issue facing drug discovery programs. Efforts are therefore being directed at developing improved 3-D kidney models. The 3-D models that are being developed are showing enhanced sensitivity and improved in vivo relevance compared to traditional 2-D kidney cell cultures.
Many improvements are being made in three-dimensional cell cultures, providing new avenues for drug safety assessment. In addition to being more relevant models compared to two-dimensional cultures, they are more cost-effective and “represent early in vitro screening tools capable of improving in vitro to in vivo translation.”
We are excited about the potential for these promising human-relevant tools in preclinical drug safety assessment and other areas of research, and the impact they will have in reducing reliance on animal models in these fields.
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Microtissues for in vitro toxicity assessment: Cost effective and in vivo relevant toxicology tools
Conventional two-dimensional (2D) cell models (adherent cells grown on cell culture plates or cells in suspension) are limited in their abilities to accurately predict clinical toxicity since they lack the fundamental complexity of in vivo tissue environments. As a result efforts are being directed towards more sophisticated multicellular three-dimensional (3D) cell models with improved in vitro to in vivo correlation
For more information see: Drug Discovery World