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Mohammadi et al. J Transl Genet Genom 2020;4:238-50 I https://doi.org/10.20517/jtgg.2020.29 Page 247
[77]
and network activities between animal models and humans . These failures clearly indicate that the hiPSC
models are superior in relation to drug development strategies. Nevertheless, one should not exclude in vivo
models, since they are still highly relevant to assessing the bioactivity of compounds and the ability of those
compounds to pass the blood-brain-barrier, which are essential to investigate before embarking on human
[22]
clinical trials. The various experimental models and their unique properties are summarized in .

CONCLUSION
2D hiPSC-derived neuronal systems generated from epilepsy patients and precise gene-editing techniques
via CRISPR/Cas9 provide powerful platforms to investigate functional consequences of gene variants and
to perform drug screening. Furthermore, cerebral organoids allow for more complex investigations of
different neural populations and 3D neural circuits. Even though the 2D model system lacks spatial and
regional complexity it is more suitable for understanding cellular pathologies. The 3D model is advantageous
to understand developmental connectivity issues between different neurons and the effect on cortical
layer development. On the down side, electrophysiological recordings and cell viability in the core of such
cerebral organoids is still challenging; since vascularization is an important factor in organoid function and
survival, various efforts are being made to improve this. Taken together, both 2D and 3D hiPSC models from
epilepsy patients are superior to cancer-based human cell models, non-human cell models or frog oocytes to
understand the underlying pathology. Lastly, hiPSC-derived neural progenitors have the future prospect of
autologous stem cell therapy, combined with precision gene editing to repair the pathogenic variants.

DECLARATIONS
Authors’ contributions
Contributed to conception and study design: Mohammadi NA, Møller RS
Drafted and revised the manuscript and figures with feedback from all of the other authors: Mohammadi NA
Contributed to generation of Figure 2 and drafting the table: Freude K, Haukedal H
Zeynep Tümer, Rikke S. Møller and Kristine Freude contributed to critical review of the manuscript: Freude
K, Tümer Z, Møller RS

Availability of data and materials
What we have of information and data are from already published artikels, meaning that they can be
available to readers.

Financial support and sponsorship
The study was supported by the Novo Nordisk Foundation (NNF19OC0058399).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

REFERENCES
1. England MJ, Liverman CT, Schultz AM, Strawbridge LM. Summary: a reprint from epilepsy across the spectrum: promoting health and