The development of drugs for human central nervous system (CNS) diseases has traditionally relied on genetically engineered mouse models (GEMMs). However, the CNS is highly complex and also, GEMMs’ phenotypes often diverge from that of human diseases. These factors represent the main obstacle to the translation of CNS drugs pre-clinical to the clinical trials.
Therefore, 3D in vitro models are useful complementary tools towards more accurate evaluation of drug candidates in pre-clinical stages, as they present an intermediate degree of complexity in terms of cell-cell and cell-matrix interactions, between the traditional 2D monolayer culture conditions and the complex brain and can be a better starting point for the analysis of the in vivo situation. We have been developing brain models using primary cultures of rat brain cells and cultures of differentiated human embryonal carcinoma cell lines and human neural stem cells.
Furthermore, we are exploring our 3D brain cell models to reveal additional layers of information, usually concealed by the high complexity of interactions that occur in vivo. Using metabolic flux analysis tools and data on 13C enrichment into intra and extracellular metabolites (NMR and GC-MS analysis) we have been quantifying the metabolic effects caused by specific insults which frequently occur in the brain.
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Frontiers in Cellular Neuroscience. 8:221
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