Experimental and Computational Methods for the Study of Cerebral Organoids: A Review
Cerebral (or brain) organoids derived from human cells have enormous potential as physiologically relevant downscaled models of the human brain. In fact, these stem cell-derived neural aggregates resemble the three-dimensional (3D) cytoarchitectural arrangement of the brain overcoming not only the u...
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Published in | Frontiers in neuroscience Vol. 13; p. 162 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Research Foundation
05.03.2019
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | Cerebral (or brain) organoids derived from human cells have enormous potential as physiologically relevant downscaled
models of the human brain. In fact, these stem cell-derived neural aggregates resemble the three-dimensional (3D) cytoarchitectural arrangement of the brain overcoming not only the unrealistic somatic flatness but also the planar neuritic outgrowth of the two-dimensional (2D)
cultures. Despite the growing use of cerebral organoids in scientific research, a more critical evaluation of their reliability and reproducibility in terms of cellular diversity, mature traits, and neuronal dynamics is still required. Specifically, a quantitative framework for generating and investigating these
models of the human brain is lacking. To this end, the aim of this review is to inspire new computational and technology driven ideas for methodological improvements and novel applications of brain organoids. After an overview of the organoid generation protocols described in the literature, we review the computational models employed to assess their formation, organization and resource uptake. The experimental approaches currently provided to structurally and functionally characterize brain organoid networks for studying single neuron morphology and their connections at cellular and sub-cellular resolution are also discussed. Well-established techniques based on current/voltage clamp, optogenetics, calcium imaging, and Micro-Electrode Arrays (MEAs) are proposed for monitoring intra- and extra-cellular responses underlying neuronal dynamics and functional connections. Finally, we consider critical aspects of the established procedures and the physiological limitations of these models, suggesting how a complement of engineering tools could improve the current approaches and their applications. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 Edited by: Ioan Opris, University of Miami, United States This article was submitted to Neural Technology, a section of the journal Frontiers in Neuroscience Reviewed by: Jennie Leach, University of Maryland, Baltimore County, United States; Kim Drnec, United States Army Research Laboratory, United States |
ISSN: | 1662-4548 1662-453X 1662-453X |
DOI: | 10.3389/fnins.2019.00162 |