Morphogenetic Designs, and Disease Models in Central Nervous System Organoids
Abstract
:1. Introduction
2. Morphogenetic Design of CNS Organoids
2.1. Cortical Organoid
2.2. Forebrain Organoid
2.3. Midbrain Organoid
2.4. Cerebellar Organoid
2.5. Spinal Cord Organoid
Author (Year) | Cell Source | Region Designed | Significance |
---|---|---|---|
Meinhardt et al. (2014) [67] | Mouse ESC | Neural tube | Spatial organization of neurons along the dorsal and ventral axis |
Ranga et al. (2016) [68] | Mouse ESC | Neural tube | Focus on extracellular matrix and cytoskeleton during patterning |
Lippmann et al. (2015) [70] | hiPSC | Neuromesoderm | Identified importance of HOX |
Ogura et al. (2018) [71] | hiPSC | Dorsal and ventral spinal cord-like tissues | Dorsal and ventral tissues generated using BMP4 and Shh signaling |
Andersen et al. (2020) [72] | hiPSC | Dorsal and ventral spinal cord-like tissues | A continuous dorsal and ventral tissue generated and connected muscle spheroids with neurons |
Mouilleau et al. (2021) [73] | hESC/hiPSC | Rostro-caudal patterning | Differentiation of motor neurons through FGF and HOX expression |
Karzbrun et al. (2021) [75] | hiPSC | Neural tube | Developed chip-based culture system for homogeneity |
Lee et al. (2022) [27] | hiPSC | Spinal cord | Generated tubular structure with functionality |
Shin et al. (2023) [76] | hPSC | Spinal cord | Necrotic core was reduced |
Gribaudo et al. (2023) [28] | hiPSC | Spinal cord | Autonomously forming AP axis |
3. CNS Organoids as Disease Models and Drug Screening Platforms
3.1. Viral Infections
3.1.1. Zika Virus (ZIKV)
3.1.2. Herpes Simplex Virus (HSV)
3.1.3. Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2)
3.2. Neurodevelopmental Diseases
3.2.1. Microcephaly
3.2.2. Autism Spectrum Disorder (ASD)
3.2.3. Developmental and Epileptic Encephalopathy (DEE)
3.3. Neurodegenerative Diseases
3.3.1. Alzheimer’s Disease (AD)
3.3.2. Parkinson’s Disease (PD)
3.3.3. Huntington’s Disease (HD)
3.3.4. Motor Neuron Diseases
3.4. CNS Tumors
Glioblastoma
4. Future Perspectives and Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Author (Year) | Cell Source | Region Designed | Significance |
---|---|---|---|
Lancaster et al. (2013, 2014) [20,31] | hPSC | Heterogenous | -First organoid -Designed microcephaly |
LaMonica et al. (2013) [33] | Fetal brain tissue | Neocortex, radial glia | Discovery of radial glia division and the involved pathways |
Quadrato et al. (2017) [34] | hPSC | Cerebral cortex | Prolonged culture of cerebral organoids led to presented diverse cells |
Lancaster et al. (2017) [35] | hiPSC/hESC | Cerebral cortex | Reproducible cerebral organoids with microfilament device |
Velasco et al. (2019) [36] | hiPSC | Cerebral cortex | Developed consistent ways to generate organoids |
Pollen et al. (2019) [37] | hiPSC/Chimpanzee-induced PSC | Cerebral cortex | Investigation of organoids among species to analyze differences |
Qian et al. (2020) [38] | hiPSC | Cerebral cortex | Developed sliced neocortical organoid system |
Uzquiano et al. (2022) [39] | hESC/hiPSC | Cerebral cortex | Single cell analysis of multiple organoids derived from multiple cell sources |
Author (Year) | Cell Source | Region Designed | Significance |
---|---|---|---|
Krefft et al. (2018) [41] | hiPSC | Early dorsal telencephalic tissues | First forebrain organoid |
Bagley et al. (2017) [42] | hiPSC | Fusion of dorsal and ventral forebrain organoid | -Production of dorsal and ventral forebrain organoid -Ability to study neurite dynamics |
Cederquist et al. (2019) [43] | hPSC | Anterior forebrain | Positional identity defined |
Gabriel et al. (2023) [44] | hiPSC | Forebrain with eye primordium | Study of multi-organ association |
Huang et al. (2021) [45] | hiPSC | “Arcuate organoids” | First efforts to create diencephalon-type forebrain organoid |
Blaess et al. (2014) [46] | hiPSC | Hypothalamus | Hypothalamus development |
Corman et al. (2018) [47] | Mice ESC | Hypothalamus | Elucidated Shh signaling and its effects with time |
Sarrafha et al. (2023) [48] | hPSC | Hypothalamus | Exploration of dopaminergic neurons |
Xiang et al. (2019) [49] | hESC | Thalamus | Fusion of cortex with thalamus organoid |
Kiral et al. (2023) [50] | hESC | Thalamus and Thalamic reticular nucleus | Generation of thalamic reticular nucleus |
Author (Year) | Cell Source | Region Designed | Significance |
---|---|---|---|
Jo et al. (2016) [52] | hPSC | Midbrain | Developed midbrain organoids with dopamine neurons that form synapses and display electrophysiological properties |
Monzel et al. (2009) [53] | Neuroepithelial stem cells | Midbrain | Glial cell differentiation |
Kwak et al. (2020) [54] | hESC | Midbrain | Defining protocols to produce homogenous midbrain organoids |
Nickels et al. (2020) [55] | hiPSC | Midbrain | Further tested protocols to generate organoids and reduce necrotic cores |
Berger et al. (2018) [56] | Neuroepithelial stem cells | Midbrain | Introduced milifluidic device to reduce necrotic regions in long term culture |
Renner et al. (2020) [57] | hPSC | Midbrain | Generated automated system for seeding, imaging, and analysis |
Author (Year) | Cell Source | Region Designed | Significance |
---|---|---|---|
Kamei et al. (2023) [59] | hiPSC | Cerebellum | Investigated cerebellar progenitors through cell transplantation |
Muguruma et al. (2015, 2018. 2020) [58,60,61] | hiPSC | Cerebellum, Purkinje cells | Ability to model cerebellar diseases |
Silva et al. (2020) [63] | hiPSC | Cerebellum | Use of a single bioreactor to mass-produce homogenous cerebellar organoids |
Nayler et al. (2021) [64] | hiPSC | Cerebellum | Air–liquid interface culture without SDF1 and FGF19 |
Chen et al. (2023) [8] | hiPSC | Cerebellum | Long-term culture of cerebellar organoids |
Atamian et al. (2024) [65] | hiPSC | Cerebellum | Analysis of cellular composition and spatial characteristics |
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Bock, M.; Hong, S.J.; Zhang, S.; Yu, Y.; Lee, S.; Shin, H.; Choi, B.H.; Han, I. Morphogenetic Designs, and Disease Models in Central Nervous System Organoids. Int. J. Mol. Sci. 2024, 25, 7750. https://doi.org/10.3390/ijms25147750
Bock M, Hong SJ, Zhang S, Yu Y, Lee S, Shin H, Choi BH, Han I. Morphogenetic Designs, and Disease Models in Central Nervous System Organoids. International Journal of Molecular Sciences. 2024; 25(14):7750. https://doi.org/10.3390/ijms25147750
Chicago/Turabian StyleBock, Minsung, Sung Jun Hong, Songzi Zhang, Yerin Yu, Somin Lee, Haeeun Shin, Byung Hyune Choi, and Inbo Han. 2024. "Morphogenetic Designs, and Disease Models in Central Nervous System Organoids" International Journal of Molecular Sciences 25, no. 14: 7750. https://doi.org/10.3390/ijms25147750