Brain organoids as models of Alzheimer’s and Parkinson’s diseases: a narrative review on perspectives for regenerative and personalized medicine
DOI:
https://doi.org/10.11606/issn.2176-7262.rmrp.2023.203797Keywords:
Organoids, Alzheimer’s disease, Parkinson’s disease, Regenerative medicine, Personalized medicineAbstract
For many years, two-dimensional (2D) cell culture has been used as a model to study diseases, having great importance in regenerative medicine, despite still having significant limitations. In order to circumvent these limitations, threedimensional (3D) cell culture proposes a more complex and sustainable organization that can be produced from adult stem cells (ASCs), embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs). The 3D culture enabled
the cultivation of cells in an environment closer to the physiological one, leading to the formation of different organspecific tissues. In other words, 3D cell culture makes it possible to create organic structures very similar to the organs of a human being, both structurally and functionally. In this way, we have what are called organoids. The use of organoids has grown exponentially in in vitro environments, allowing the analysis and observation of the various existing physiological phenomena. As an example, we can mention the brain organoids (“mini-brains”) reproduced in vitro, seeking to delineate the peculiarities and complexities of the human brain, in order to understand some neurological dysfunctions that affect this system, such as the two main neurodegenerative diseases: Alzheimer’s and Parkinson’s Diseases. Therefore, brain organoids may allow a remarkable advance in regenerative medicine applied to neurodegenerative diseases, as these “mini-brains” can be produced from the patient’s own cells. This will allow for personalized interventions, such as drug testing, in order to define what would be the best drug treatment. Consequently, this technology can enable more efficient and individualized therapies - which is fundamental for Personalized Medicine.
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References
Neal, J. T., & Kuo, C. J. (2016). Organoids as models for neoplastic transformation. Annual Review of Pathology: Mechanisms of Disease, 11, 199-220.
Rozich, N. S., Blair, A. B., & Burkhart, R. A. (2020). Organoids: a model for precision medicine. In Precision Medicine for Investigators, Practitioners and Providers, (Elsevier), pp. 123–129.
Clevers, H. (2016). Modeling development and disease with organoids. Cell, 165(7), 1586-1597.
Fang, Y., & Eglen, R. M. (2017). Three-dimensional cell cultures in drug discovery and development. Slas discovery: Advancing Life Sciences R&D, 22(5), 456-472.
Huch, M., Gehart, H., Van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M. et al. (2015). Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell, 160(1-2), 299-312.
Schutgens, F., & Clevers, H. (2020). Human organoids: tools for understanding biology and treating diseases. Annual Review of Pathology: Mechanisms of Disease, 15, 211-234.
Sato, T., Stange, D. E., Ferrante, M., Vries, R. G., Van Es, J. H., Van Den Brink, S. et al. (2011). Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology, 141(5), 1762-1772.
Hu, H., Gehart, H., Artegiani, B., LÖpez-Iglesias, C., Dekkers, F., Basak, O. et al. (2018). Long-term expansion of functional mouse and human hepatocytes as 3D organoids. Cell, 175(6), 1591-1606.
Chang, Y., Kim, J., Park, H., Choi, H., & Kim, J. (2020). Modelling neurodegenerative diseases with 3D brain organoids. Biological Reviews, 95(5), 1497-1509.
Venkataraman, L., Fair, S. R., McElroy, C. A., Hester, M. E., & Fu, H. (2020). Modeling neurodegenerative diseases with cerebral organoids and other three-dimensional culture systems: Focus on Alzheimer’s disease. Stem Cell Reviews and Reports, 1-22.
Fyfe, I. (2021). Brain organoids shed light on APOE genotype and Alzheimer disease pathology. Nature Reviews Neurology, 17(1), 1-2.
Papaspyropoulos, A., Tsolaki, M., Foroglou, N., & Pantazaki, A. A. (2020). Modeling and targeting Alzheimer’s disease with organoids. Frontiers in pharmacology, 11, 396.
Galet, B., Cheval, H., & Ravassard, P. (2020). Patient-derived midbrain organoids to explore the molecular basis of Parkinson's disease. Frontiers in Neurology, 1005.
Smits, L. M., Reinhardt, L., Reinhardt, P., Glatza, M., Monzel, A. S., Stanslowsky, N. et al. (2019). Modeling Parkinson’s disease in midbrain-like organoids. NPJ Parkinson's disease, 5(1), 1-8.
Wulansari, N., Darsono, W. H. W., Woo, H. J., Chang, M. Y., Kim, J., Bae, E. J., ... & Lee, S. H. (2021). Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson’s disease-linked DNAJC6 mutations. Science Advances, 7(8), 1540.
Azar, J., Bahmad, H. F., Daher, D. et al. (2021). The use of stem cell-derived organoids in disease modeling: an update. Int J Mol Sci 22, doi: https://doi.org/10.3390/ijms22147667
Fatehullah, A., Tan, S. H., & Barker, N. (2016). Organoids as an in vitro model of human development and disease. Nature cell biology, 18(3), 246-254.
Krokker, L., Szabó, B., Németh, K., Tóháti, R., Sarkadi, B., Mészáros, K. et al. (2021). Three Dimensional Cell Culturing for Modeling Adrenal and Pituitary Tumors. Pathology and Oncology Research, 27.
Liu, L., Yu, L., Li, Z., Li, W., & Huang, W. (2021). Patient-derived organoid (PDO) platforms to facilitate clinical decision making. Journal of Translational Medicine, 19(1), 1-9.
Nanki, Y., Chiyoda, T., Hirasawa, A., Ookubo, A., Itoh, M., Ueno, M. et al. (2020). Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing. Scientific Reports, 10(1), 1-11.
Pernik, M. N., Bird, C. E., Traylor, J. I., Shi, D. D., Richardson, T. E., McBrayer, S. K., & Abdullah, K. G. (2021). Patient-derived cancer organoids for precision oncology treatment. Journal of Personalized Medicine, 11(5), 423.
Takahashi, T. (2019). Organoids for drug discovery and personalized medicine. Annual review of pharmacology and toxicology, 59, 447-462.
Verjans, E. T., Doijen, J., Luyten, W., Landuyt, B., & Schoofs, L. (2018). Three‐dimensional cell culture models for anticancer drug screening: Worth the effort?. Journal of cellular physiology, 233(4), 2993-3003.
Cosset, E., Locatelli, M., Marteyn, A., Lescuyer, P., Antonia, F. D., Mor, F. M. et al. (2019). Human neural organoids for studying brain cancer and neurodegenerative diseases. JoVE (Journal of Visualized Experiments), (148).
Wray, S. (2021). Modelling neurodegenerative disease using brain organoids. In Seminars in Cell & Developmental Biology (Vol. 111, pp. 60-66). Academic Press.
Nie, J., & Hashino, E. (2017). Organoid technologies meet genome engineering. EMBO reports, 18(3), 367-376.
Wang, Z., Wang, S. N., Xu, T. Y., Miao, Z. W., Su, D. F., & Miao, C. Y. (2017). Organoid technology for brain and therapeutics research. CNS neuroscience & therapeutics, 23(10), 771-778.
De Oliveira, M., De Sibio, M. T., Costa, F. A., & Sakalem, M. E. (2021). Airway and Alveoli Organoids as Valuable Research Tools in COVID-19. ACS Biomaterials Science & Engineering, 7(8), 3487-3502.
Song, L., Yuan, X., Jones, Z., Griffin, K., Zhou, Y., Ma, T., & Li, Y. (2019). Assembly of human stem cell-derived cortical spheroids and vascular spheroids to model 3-D brain-like tissues. Scientific reports, 9(1), 1-16.
Janssens, S., Schotsaert, M., Manganaro, L., Dejosez, M., Simon, V., García‐Sastre, A., & Zwaka, T. P. (2019). FACS‐Mediated Isolation of Neuronal Cell Populations From Virus‐Infected Human Embryonic Stem Cell–Derived Cerebral Organoid Cultures. Current protocols in stem cell biology, 48(1), e65.
Magno, V., Meinhardt, A., & Werner, C. (2020). Polymer hydrogels to guide organotypic and organoid cultures. Advanced Functional Materials, 30(48), 2000097.
Choi, S. H., Kim, Y. H., Hebisch, M., Sliwinski, C., Lee, S., D’Avanzo, C. et al. (2014). A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature, 515(7526), 274-278.
Cohen, R. M., Rezai-Zadeh, K., Weitz, T. M., Rentsendorj, A., Gate, D., Spivak, I. et al. (2013). A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric aβ, and frank neuronal loss. Journal of Neuroscience, 33(15), 6245-6256.
Beiske, A. G., Loge, J. H., Rønningen, A., & Svensson, E. (2009). Pain in Parkinson’s disease: prevalence and characteristics. Pain, 141(1-2), 173-177. doi: https://doi.org/10.1016/j.pain.2008.12.004
Kim, H., Park, H. J., Choi, H., Chang, Y., Park, H., Shin, J. et al. (2019). Modeling G2019S-LRRK2 sporadic Parkinson's disease in 3D midbrain organoids. Stem Cell Reports, 12(3), 518-531.
Sloan, S.A., Andersen, J., Pașca, A.M. et al.(2018). Generation and assembly of human brain region–specific three-dimensional cultures. Nat Protoc 13, 2062–2085 . https://doi.org/10.1038/s41596-018-0032-7
Lancaster, M., Knoblich, J. (2014). Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc 9, 2329–2340. https://doi.org/10.1038/nprot.2014.158
A Armstrong R. (2019) Risk factors for Alzheimer's disease. Folia Neuropathol.;57(2):87-105. doi: 10.5114/fn.2019.85929. PMID: 31556570.
Mendez MF. (2019) Early-onset Alzheimer Disease and Its Variants. Continuum (Minneap Minn). Feb;25(1):34-51. doi: 10.1212/CON.0000000000000687.
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Copyright (c) 2023 Raysa Taynara Vasconcelos de Souza, Pedro Henrique Gomes Santana, Ricardo Cambraia Parreira, Lucas Felipe Oliveira, Adrieli Oliveira Raminelli, Bruno Lemes Marques, Daniel Mendes Filho
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