Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling
With 100 billion neurons and 100 trillion synapses, the human brain is not just the most complex organ in the human body, but has also been described as “the most complex thing in the universe.” The limited availability of human living brain tissue for the study of neurogenesis, neural processes and...
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doaj-7d199d9ed22943c4aa3b7a8503c294952020-11-25T01:36:59ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-04-011310.3389/fncel.2019.00129440950Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System ModellingDario Pacitti0Dario Pacitti1Riccardo Privolizzi2Bridget E. Bax3Molecular and Clinical Sciences Research Institute, St George’s, University of London, London, United KingdomCollege of Medicine and Health, St Luke’s Campus, University of Exeter, Exeter, United KingdomGene Transfer Technology Group, Institute for Women’s Health, University College London, London, United KingdomMolecular and Clinical Sciences Research Institute, St George’s, University of London, London, United KingdomWith 100 billion neurons and 100 trillion synapses, the human brain is not just the most complex organ in the human body, but has also been described as “the most complex thing in the universe.” The limited availability of human living brain tissue for the study of neurogenesis, neural processes and neurological disorders has resulted in more than a century-long strive from researchers worldwide to model the central nervous system (CNS) and dissect both its striking physiology and enigmatic pathophysiology. The invaluable knowledge gained with the use of animal models and post mortem human tissue remains limited to cross-species similarities and structural features, respectively. The advent of human induced pluripotent stem cell (hiPSC) and 3-D organoid technologies has revolutionised the approach to the study of human brain and CNS in vitro, presenting great potential for disease modelling and translational adoption in drug screening and regenerative medicine, also contributing beneficially to clinical research. We have surveyed more than 100 years of research in CNS modelling and provide in this review an historical excursus of its evolution, from early neural tissue explants and organotypic cultures, to 2-D patient-derived cell monolayers, to the latest development of 3-D cerebral organoids. We have generated a comprehensive summary of CNS modelling techniques and approaches, protocol refinements throughout the course of decades and developments in the study of specific neuropathologies. Current limitations and caveats such as clonal variation, developmental stage, validation of pluripotency and chromosomal stability, functional assessment, reproducibility, accuracy and scalability of these models are also discussed.https://www.frontiersin.org/article/10.3389/fncel.2019.00129/fullCNShiPSChuman neuronshuman glianeurogenesisneurological disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dario Pacitti Dario Pacitti Riccardo Privolizzi Bridget E. Bax |
spellingShingle |
Dario Pacitti Dario Pacitti Riccardo Privolizzi Bridget E. Bax Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling Frontiers in Cellular Neuroscience CNS hiPSC human neurons human glia neurogenesis neurological disorders |
author_facet |
Dario Pacitti Dario Pacitti Riccardo Privolizzi Bridget E. Bax |
author_sort |
Dario Pacitti |
title |
Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling |
title_short |
Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling |
title_full |
Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling |
title_fullStr |
Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling |
title_full_unstemmed |
Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling |
title_sort |
organs to cells and cells to organoids: the evolution of in vitro central nervous system modelling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2019-04-01 |
description |
With 100 billion neurons and 100 trillion synapses, the human brain is not just the most complex organ in the human body, but has also been described as “the most complex thing in the universe.” The limited availability of human living brain tissue for the study of neurogenesis, neural processes and neurological disorders has resulted in more than a century-long strive from researchers worldwide to model the central nervous system (CNS) and dissect both its striking physiology and enigmatic pathophysiology. The invaluable knowledge gained with the use of animal models and post mortem human tissue remains limited to cross-species similarities and structural features, respectively. The advent of human induced pluripotent stem cell (hiPSC) and 3-D organoid technologies has revolutionised the approach to the study of human brain and CNS in vitro, presenting great potential for disease modelling and translational adoption in drug screening and regenerative medicine, also contributing beneficially to clinical research. We have surveyed more than 100 years of research in CNS modelling and provide in this review an historical excursus of its evolution, from early neural tissue explants and organotypic cultures, to 2-D patient-derived cell monolayers, to the latest development of 3-D cerebral organoids. We have generated a comprehensive summary of CNS modelling techniques and approaches, protocol refinements throughout the course of decades and developments in the study of specific neuropathologies. Current limitations and caveats such as clonal variation, developmental stage, validation of pluripotency and chromosomal stability, functional assessment, reproducibility, accuracy and scalability of these models are also discussed. |
topic |
CNS hiPSC human neurons human glia neurogenesis neurological disorders |
url |
https://www.frontiersin.org/article/10.3389/fncel.2019.00129/full |
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