iBET has long-term expertise in developing advanced cell models for neural, hepatic and cancer research
We deliver novel and improved cell models for drug discovery, toxicology and pre-clinical research by integrating bioprocessing development and molecular cell biology techniques
Neural Cell Models
We have been developing neural 3D cell models – neurospheroids -, employing hNSC (human neural stem cells) from several sources, including hiPSC (human-induced pluripotent stem cells). Our neurospheroids are composed by neurons, astrocytes, and oligodendrocytes. We have seen that neurons and astrocytes are functional and present metabolic compartmentalization characteristic of brain tissue. Also, specific features of the brain microenvironment are recapitulated, namely the presence of typical neuronal receptors and channels, as well as the extracellular matrix composition.
Concerning disease modelling, we are focused on neurological diseases in which extracellular compartment dynamics plays a role in the pathological features (e.g. lysosomal storage diseases, Alzheimer’s disease, brain injuries).
Complementarily, we employ advanced imaging tools and Metabolic Flux Analysis tools for in depth characterization of neuronal activity and of metabolic fluxes between neurons and astrocytes in healthy and disease situations, as well as in response to drugs.
Employing our strategy for primary culture of human hepatocyte spheroids in perfusion bioreactors, investigational drug behaviour can be recapitulated and interpreted for over a month (hepatic metabolism and toxicity). Thus, we’ve extended our methodology to a panel of human hepatic cell lines, including HepaRG, and for co-culture including non-parenchymal cells.
We work on hepatic differentiation of hiPSC (human-induced pluripotent stem cells) from different backgrounds, including from patients with genetic metabolic disorders. Recently, we’ve extended the application of our human hepatic 3D cell models to infectious diseases caused by viral and parasitic agents.
We have implemented a platform for the generation of tumour spheroids from a large panel of human cancer cell lines, employing dynamic suspension culture systems.
We are working in the development and characterization of co-culture cancer cell models (tumour cells, fibroblasts, and immune cells – macrophages), in which tumour microenvironment features are depicted, such as an immunosuppressive microenvironment.
We have recently extended our platform to ex-vivo modelling, implementing long-term cultures of patient-derived tumour explants (breast, ovarian and colorectal cancer) in which tissue vitality, cell composition, morphology, and genetic status are mainly maintained after 1 month of culture.
We are now working in several translational projects, involving clinical teams at Instituto Português de Oncologia Francisco Gentil (IPOLFG), under the umbrella of iNOVA4Health that aim at discovering drug resistance biomarkers and predicting patient outcome.