Generation of mature human brain organoids for the study of neurodegenerative diseases
Commonly used acronym: MatBOneurodeg
Scope of the method
- Human health
- Basic Research
- Translational - Applied Research
- In vitro - Ex vivo
- Human derived cells / tissues / organs
- HUman brain organoids
- adult human brain features
- Alzheimer's disease
- Stem cell methods
The maturation of the human brain shows species-specific differences of neoteny when compared to lower mammals. This process encompass a time window that expands from late embryonic stages to early adolescence. Major features of brain maturation are the acquisition of phenotypic complex traits such as axonal and dendritic trees and the presence of dendritic spines which correlate with higher functionality and connectivity of the neurons. Interestingly, human transcriptomic data has shown a narrow time window from the birth of the individual to the first two years of life where major transcriptomic changes occur. Here, we address human-specific species features of brain maturation using a multicellular human in vitro brain organoid model composed of neurons and glia cell types. Long-term human brain organoids are analysed functionally for the acquisition of mature neuronal phenotypes to understand the time line of maturation compared to the in vivo situation. Further, we show that long-term human brain organoids acquire features characteristic of the adult human brain and that they can recapitulate hallmarks of AD in vitro.
- - Human stem cell culture facility,
- - Bioreactor for the growth of long-term human brain organoids.
- Still in development
- History of use
Pros, cons & Future potential
This improved method for the generation of long-term human brain organoids recapitulates human brain maturation features including the expression of genes present in the adult human brain.
Time is a limiting factor, it requires an extensive amount of time (long-term culture) to achive the expression of mature brain adult features in human brain organoids.
Modifications of the system are being tested such as the exposure to extrinsic cues or the modification of intrinsic factors.
The generation of an adult human brain organoid model would be instrumental for the study of neurodegenerative diseases in a reductionist manner in a purely in vitro set up.
References, associated documents and other information
- Magni, M., Bossi, B., Conforti, P., Galimberti, M., Dezi, F., Lischetti, T., He, X., Barker, R., Zuccato, C., Espuny-Camacho, I., *., and Cattaneo, E*. Brain regional identity and cell type specificity landscape of human cortical organoid models. Int J Mol Sci 2022: doi.org/10.3390/ijms232113159.
- Espuny-Camacho, I., Arranz Mendiguren, A., Fiers, M., Snellinx, A., Corthout, N., Munch, S., Leroy, K., Brion, J.P., Vanderhaghen, P., De Strooper B. (2017). Hallmarks of Alzheimer’s disease in stem cell-derived human neurons transplanted into mouse brain. Neuron 93 (5), 1066-1081. (SCI impact factor 15,982).
- Espuny-Camacho, I., Michelsen, K.A., Gall, D., Linaro, D., Hasche, A., Bonnefont, J., Bali, C., Orduz, D., Bilheu, A., Herpoel, A., Lambert, N., Gaspard, N., Perón, S., Schiffmann, S.N., Giugliano, M., Gaillard, A., Vanderhaeghen, P. (2013). Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivo. Neuron 77 (3), 440-56. Preview and Featured article in Neuron. (SCI impact factor 15,982).
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Contact personIra Espuny Camacho
OrganisationsUniversity of Liège (ULiège)