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 of neurons, astrocytes, and oligodendrocytes. We have seen that neurons and astrocytes are functional and present metabolic compartmentalization characteristic of brain tissue. Specific features of the brain microenvironment are recapitulated, namely the presence of typical neuronal receptors and channels, as well as the extracellular matrix composition.
Current projects include model refinement for incorporation of microglia (cell line and hiPSC-derived) to address neuroinflammation and innate immunity in disease, response to therapeutic viral vectors and aging.
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, metabolic flux analysis and multi-omics 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 behavior can be recapitulated and interpreted for over a month (hepatic metabolism and toxicity). We’ve extended our methodology to a panel of human hepatic cell lines, including HepG2 and HepaRG.
We work on hepatic differentiation of hiPSC (human-induced pluripotent stem cells) from different backgrounds, including from patients with genetic metabolic disorders.
In recent years, we have extended the application of our human hepatic 3D cell models to infectious diseases caused by viral and parasitic agents, and are refining the model to incorporate immune cells.
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 have developed a co-culture cancer cell model platform (composed of tumor cells, fibroblasts, and immune cells – macrophages), in which tumour microenvironment features are depicted and there is built up of immunosuppressive microenvironments. This platform is being applied for preclinical testing of immunotherapeutics targeting the innate compartment of the immune infiltrate, in collaboration with industrial partners.
We have extended our platform to ex-vivo modelling, implementing long-term cultures of patient-derived tumor explants (breast, ovarian and colorectal cancer) in which tissue architecture, cell composition, cell morphology and genetic status, as well as key signaling pathways governing carcinogenesis, are mainly maintained up to 1 month of culture. We are applying these patient-derived models 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.