Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Aug 3:16:1173433.
doi: 10.3389/fnmol.2023.1173433. eCollection 2023.

Development of brain organoid technology derived from iPSC for the neurodegenerative disease modelling: a glance through

Amirah Syamimi Jusop  1 , Kalaiselvaan Thanaskody  1 , Gee Jun Tye  2 , Sylvia Annabel Dass  2 , Wan Safwani Wan Kamarul Zaman  3 , Fazlina Nordin  1
Affiliations
Review

Development of brain organoid technology derived from iPSC for the neurodegenerative disease modelling: a glance through

Amirah Syamimi Jusop et al. Front Mol Neurosci. .

Abstract

Neurodegenerative diseases are adult-onset neurological conditions that are notoriously difficult to model for drug discovery and development because most models are unable to accurately recapitulate pathology in disease-relevant cells, making it extremely difficult to explore the potential mechanisms underlying neurodegenerative diseases. Therefore, alternative models of human or animal cells have been developed to bridge the gap and allow the impact of new therapeutic strategies to be anticipated more accurately by trying to mimic neuronal and glial cell interactions and many more mechanisms. In tandem with the emergence of human-induced pluripotent stem cells which were first generated in 2007, the accessibility to human-induced pluripotent stem cells (hiPSC) derived from patients can be differentiated into disease-relevant neurons, providing an unrivaled platform for in vitro modeling, drug testing, and therapeutic strategy development. The recent development of three-dimensional (3D) brain organoids derived from iPSCs as the best alternative models for the study of the pathological features of neurodegenerative diseases. This review highlights the overview of current iPSC-based disease modeling and recent advances in the development of iPSC models that incorporate neurodegenerative diseases. In addition, a summary of the existing brain organoid-based disease modeling of Alzheimer's disease was presented. We have also discussed the current methodologies of regional specific brain organoids modeled, its potential applications, emphasizing brain organoids as a promising platform for the modeling of patient-specific diseases, the development of personalized therapies, and contributing to the design of ongoing or future clinical trials on organoid technologies.

Keywords: Alzheimer’s disease; assembloids; brain organoids; disease modeling; induced pluripotent stem cells (iPSCs); neurodegenerative disease.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Graphical Abstract. An overview of the iPSC-derived organoids for neurodegenerative disease modeling. Created with Biorender.com.
Figure 2
Figure 2
The potential application of iPSCs in understanding neurodegenerative diseases. iPSCs can be reprogrammed from various somatic cells and differentiated into multiple cell lineages because they possess unique properties of self-renewal and pluripotency. There are many applications of iPSCs in the fields of gene therapy, disease modeling, and drug discovery. Created with Biorender.com.
Figure 3
Figure 3
Neural stem cells are tripotent cells that can differentiate into neural lineage cell subtypes like neurons, oligodendrocytes, and astrocytes. Created with Biorender.com.
Figure 4
Figure 4
Achievements and milestones in iPSC research. Timeline showing the achievements of iPSC technology since 1976, divided into general milestones and time points when neural derivatives were first successfully generated.
Figure 5
Figure 5
Limitation, compatibility of organoids and benefit of disease modeling with iPSC-derived organoid.
See this image and copyright information in PMC

References

    1. Abdullah A. I., Pollock A., Sun T. (2012). The path from skin to brain: generation of functional neurons from fibroblasts. Mol. Neurobiol. 45, 586–595. doi: 10.1007/s12035-012-8277-6, PMID: - DOI - PMC - PubMed
    1. Abud E. M., Ramirez R. N., Martinez E. S., Healy L. M., Nguyen C. H. H., Newman S. A., et al. . (2017). iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94, 278–293.e9. doi: 10.1016/j.neuron.2017.03.042, PMID: - DOI - PMC - PubMed
    1. AlFatah Mansour A., Tiago Gonçalves J., Bloyd C. W., Li H., Fernandes S., Quang D., et al. . (2018). An in vivo model of functional and vascularized human brain organoids HHS public access author manuscript. Nat. Biotechnol. 36, 432–441. doi: 10.1038/nbt.4127, PMID: - DOI - PMC - PubMed
    1. Amin N. D., Paşca S. P. (2018). Building models of brain disorders with three-dimensional organoids. Neuron 100, 389–405. doi: 10.1016/j.neuron.2018.10.007, PMID: - DOI - PubMed
    1. Arber C., Lovejoy C., Harris L., Willumsen N., Alatza A., Casey J. M., et al. . (2021). Familial Alzheimer’s disease mutations in PSEN1 Lead to premature human stem cell neurogenesis. Cell Rep. 34:108615. doi: 10.1016/j.celrep.2020.108615, PMID: - DOI - PMC - PubMed