Abstract
Cerebral organoid, also known as brain organoid, describes an artificially grown, in vitro, miniature organ resembling the human brain. Cerebral organoids are created by culturing pluripotent stem cells (PSC) in a rotational bioreactor over the course of months. Within this time, the ability of PSC to self-organize and differentiate into three-dimensional (3D) brain-like structures enables scientists to gain new insights into development processes and functional features of the human brain. Cerebral organoids have the remarkable ability to recapitulate key events of human brain development. Specifically, the self-assembly and formation of complex 3D cellular systems with a minimum of extrinsic guidance are fascinating. Interestingly, cerebral organoids generate multiple brain-specific cell types in a temporal and spatial pattern similar to the human brain. Cerebral organoids significantly improve our understanding of brain structures and functions and enable a better understanding of neurodevelopmental and neurodegenerative diseases. However, major concerns exist in relation to cerebral organoid research. Specifically, the closer the model might get to a functioning human brain, the more ethical questions are raised. The ethical discourse will be necessary to define guidelines.
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Notes
- 1.
Kuzawa et al. (2014), “Metabolic costs and evolutionary implications of human brain development”.
- 2.
Mariani et al. (2015), “FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders”.
- 3.
Coe et al. (2012), “The genetic variability and commonality of neurodevelopmental disease”.
- 4.
Takahashi et al. (2007), “Induction of pluripotent stem cells from adult human fibroblasts by defined factors”.
- 5.
Thomson et al. (1998), “Embryonic stem cell lines derived from human blastocysts”.
- 6.
de Wert and Mummery (2003), “Human embryonic stem cells: research, ethics and policy”.
- 7.
Takahashi et al. (2007), “Induction of pluripotent stem cells from adult human fibroblasts by defined factors”.
- 8.
Brennand et al. (2011), “Modelling schizophrenia using human induced pluripotent stem cells”.
- 9.
Prots et al. (2018), “U-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies”.
- 10.
Lancaster et al. (2013), “Cerebral organoids model human brain development and microcephaly”.
- 11.
Qian et al. (2017), “Using brain organoids to understand Zika virus-induced microcephaly”.
- 12.
Klaus et al. (2019), “Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia”.
- 13.
Lancaster et al. (2013), “Cerebral organoids model human brain development and microcephaly”.
- 14.
The neuro-ectoderm layer consists of cells derived from the ectoderm, the formation of which is the first step in the development of the nervous system and in which the neural tube is developed in the embryo.
- 15.
Long and Huttner (2019), “How the extracellular matrix shapes neural development”.
- 16.
Lancaster et al. (2013), “Cerebral organoids model human brain development and microcephaly”.
- 17.
Pasca et al. (2015), “Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture”.
- 18.
Sakaguchi et al. (2015), “Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue”.
- 19.
Quadrato and Arlotta (2017), “Present and future of modeling human brain development in 3D organoids”.
- 20.
Glia, also called neuroglia, are non-neuronal cells in the central nervous system that do not generate electrical impulses but make a decisive contribution to homeostasis, functionality, and protection of neurons.
- 21.
Kadoshima et al. (2013), “Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell–derived neocortex”.
- 22.
Quadrato et al. (2017), “Cell diversity and network dynamics in photosensitive human brain organoids”.
- 23.
Quadrato and Arlotta (2017), “Present and future of modeling human brain development in 3D organoids”.
- 24.
Von Bartheld Christopher and Bahney (2016), “The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting”.
- 25.
Abud et al. (2017), “iPSC-derived human microglia-like cells to study neurological diseases”.
- 26.
Mansour et al. (2018), “An in vivo model of functional and vascularized human brain organoids”.
- 27.
Kanton et al. (2019), “Organoid single-cell genomic atlas uncovers human-specific features of brain development”.
- 28.
Camp et al. (2015), “Human cerebral organoids recapitulate gene expression programs of fetal neocortex development”.
- 29.
Quadrato et al. (2017), “Cell diversity and network dynamics in photosensitive human brain organoids”.
- 30.
Trujillo et al. (2019), “Complex oscillatory waves emerging from cortical organoids model early human brain network development”.
- 31.
Birey et al. (2017), “Assembly of functionally integrated human forebrain spheroids”.
- 32.
Mansour et al. (2018), “An in vivo model of functional and vascularized human brain organoids”.
- 33.
Andersen et al. (2020), “Generation of Functional Human 3D Cortico-Motor Assembloids”.
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Zagha, N., Winner, B. (2022). Development of Brain Organoids with Genome-Edited iPSC-Derived Brain Cells. In: Dederer, HG., Hamburger, D. (eds) Brain Organoids in Research and Therapy. Advances in Neuroethics. Springer, Cham. https://doi.org/10.1007/978-3-030-97641-5_2
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