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Current Methods for Modeling Developmental Disorders Using Organoids Derived From Human Pluripotent Stem Cells 

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Ana Rita Gomes

Ana Rita Gomes

Universidade de Lisboa, Instituto Superior Técnico, i4HB-Institute for Health and Bioeconomy, Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences and Associate Laboratory

Ana Rita Gomes is a PhD candidate in Bioengineering – Cell Therapies and Regenerative Medicine at Instituto Superior Técnico, University of Lisbon. Ana Rita has her MSc in Biological Engineering from Instituto Superior Técnico, University of Lisbon. Her research is focused on the study of organoid biology and process engineering strategies that combine to develop region specific brain organoids, mainly those containing ventral and dorsal forebrain characteristic neurons, as well as cerebellum characteristic cells, from human induced pluripotent stem cells (hiPSCs). The main objective is to use the organoids platform for modeling the neurodevelopmental disorder, Rett Syndrome (RTT).  

Maria Margarida Diogo

Maria Margarida Diogo

Universidade de Lisboa, Instituto Superior Técnico, i4HB-Institute for Health and Bioeconomy, Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences and Associate Laboratory

Dr. Margarida Diogo is an Assistant Professor at Instituto Superior Técnico, University of Lisbon. Dr. Margarida received her PhD in Biotechnology, from Instituto Superior Técnico, University of Lisbon. Her research activities are focused on the development of innovative advanced models of healthy and diseased human tissues from induced pluripotent stem cells (hiPSCs) and their applications for personalized medicine; in particular, for disease modelling and for the development of drug screening and toxicology assays. Present ongoing projects include the development of region-specific brain organoids and assembloids from patient-specific hiPSCs for modelling neurodevelopmental diseases and drug screening and the engineering of novel heart organoids for cardiotoxicology assays.

Tiago G. Fernandes

Tiago G. Fernandes

Universidade de Lisboa, Instituto Superior Técnico, i4HB-Institute for Health and Bioeconomy, Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences and Associate Laboratory

Dr. Tiago Fernandes is an Assistant Professor at Instituto Superior Técnico, University of Lisbon. Dr. Tiago received his PhD in Biotechnology, from Instituto Superior Técnico, University of Lisbon. His work is focused on providing an integrated platform for bringing together engineering and biology in order to accelerate progress towards designing stem cell fate and its microenvironment. The development of artificial cellular niches for studying the mechanisms that affect human stem cell pluripotency is of foremost importance and represents a major goal of his research. Human pluripotent stem cells are used as model systems to establish in vitro artificial microenvironments that better mimic the extracellular environment. A systems-based approach is expected to contribute to the development of innovative cell culture models that better reflect in vivo function, and the final goal is to generate cells and tissues to advance our understanding of biology and tissue regeneration, which will lead to further development of cell-based therapies.

Collection Overview

Organoids derived from human pluripotent stem cells have emerged as a novel platform for modeling and investigating several human-specific diseases, particularly developmental disorders. Human Pluripotent Stem Cells (hPSCs) are guided through a succession of cell fate decisions to generate diverse specialized cell types reminiscent of the three germ layers: ectoderm, mesoderm and endoderm. In vitro, these specialized cells are able to organize into complex 3D structures that mimic specific organs, and faithfully recapitulate several aspects of human development. The combination of bioengineering strategies with advances in molecular biology have enhanced organoid complexity and maturity, and these are now able to display functional characteristics of the resembling organs. hPSCs can be patient derived, preserving all the genomic alterations associated with the disorder, or genetically engineered with specific disease alterations. For example, brain, gut, retina, kidney, or liver hPSCs-derived organoids allow the study of global transcriptional or epigenetic changes occurring during early human development disorders, facilitating the research of new biomarkers or the development of novel therapeutic strategies. Autism spectrum disorders, Bilirubin, Hermansky-Pudlak or Rett syndromes are some examples of developmental disorders that could benefit from the combination of both hPSCs and organoid strategies, allowing the implementation of translational applications, disease modeling, and personalized medicine. 

In this collection, we present several methodologies for organoid hPSC-derived culture, which results in the study and modulation of distinct developmental disorders. These protocols will provide detailed information regarding the relevant procedures and engineering strategies for culturing 3D systems. Additionally, it will be included relevant analytical methodology strategies for the study of the disease mechanisms or for possible translational approaches. 

 

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Generating Self-Assembling Human Heart Organoids Derived from Pluripotent Stem Cells
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Generating Self-Assembling Human Heart Organoids Derived from Pluripotent Stem Cells

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Cited by 16

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2021

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