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Focus Area Biology and Engineering of Pluripotent Stem Cells

Stem Cell Advanced Tissue Models Lab

PI: Margarida Diogo

Engineering of central nervous system models from hiPSCs for neurotoxicology assays

3D size-controlled aggregates of neural precursors derived from hiPSCs are used for studying the effect of neurotoxicants (e.g. valproic acid) and other compounds that may interfere with the early development of the central nervous system, in particular with the formation of the neural tube. 3D microarray culture systems for expansion, neural induction and neuronal differentiation of hiPSCs are also being developed for high-throughput screening of the effect of these and other molecules in collaboration with Jon Dordick’s lab at RPI, USA.

Engineering of brain region-specific organoids from hiPSCs for modeling of neural diseases and drug screening

Patient specific hiPSCs are being applied for the development of in vitro models of rare neurodevelopmental disorders and neurodegenerative diseases for studying these diseases using more realist, complex and functional models of the human brain than the traditional models based on 2D cultures of neural cell lines. In particular, brain-region specific forebrain organoids are being developed from Rett syndrome (RTT) hiPSCs to more faithfully recapitulate the formation and maturation of different brain regions affected by RTT and reveal molecular, cellular, structural and functional alterations that previous RTT models failed to capture. These innovative models will be used to evaluate the effect of drug candidates to rescue the neuronal functional phenotype.

Engineering of cardiovascular organoids from hiPSCs for toxicology assays and cardiac disease modelling

A microwell platform was developed for standardized production of 3D aggregates of cardiomyocytes (CMs) from hiPSCs and characterized by transcriptomic analysis, revealing a faster maturation and a more functional profile of the CMs generated in this particular 3D environment when compared to the standard 2D cultures of CMs. These 3D aggregates have been successfully applied for modelling of hypertrophic cardiomyopathy in collaboration with Maria Carmo Fonseca’s lab at IMM. A more complex cardiovascular organoid containing the different types of cells and interactions that are present in the cardiac tissue is presently being engineered from hiPSCs envisaging the development of a cardiac model with additional functionality, maturity and physiological relevance. This organoid model will be used for cardiotoxicology assays.


PhD holders

Maria Margarida Fonseca Rodrigues Diogo, Stem Cell-based Advanced Tissue Models for Personalized Medicine (Keywords: human pluripotent stem cells, neural and cardiac differentiation, organoids, disease modelling, drug screening)

Mariana da Mota Veiga de Araújo Branco, Novel heart organoids for cardiotoxicology assays and cardiac disease modelling (Keywords: Organoids, Cardiac differentiation, Toxicology Assays)

PhD students

Ana Rita Carreira Baptista Gomes, Engineering region-specific brain organoids from human induced pluripotent stem cells for disease modeling of Rett syndrome, (Keywords: Organoids, Neural differentiation, Rett Syndrome)

André Lopes Rodrigues, 3D Cellular Microarray Platforms for human pluripotent stem cell culture and toxicology screenings (Keywords: 3D Cell Microarrays, High-throughput screening (HTS), Toxicology assays)

Medical doctor (MD), PhD student

João Carreira, Chromosome 6 replacement in Human Embryonic Stem Cells (hESCs) (Keywords: Human pluripotent stem cells, immune rejection, transplantation)

Key collaborators

Ana M Sebastião (IMM/FMUL), Sofia Duarte (Centro Hospitalar Universitário de Lisboa), Jon S Dordick (Rensselaer Polytechnic Institute, USA), Perpétua Pinto do Ó (i3S/UPorto), Leonilde Moreira (iBB/IST), Maria Carmo-Fonseca (IMM/FMUL), Domingos Henrique (IMM/FMUL)