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Review
. 2023 Jan 30;13(2):260.
doi: 10.3390/biom13020260.

Modeling Autism Spectrum Disorders with Induced Pluripotent Stem Cell-Derived Brain Organoids

John Lenon de Souza Santos  1   2 , Cecília de Almeida Araújo  2   3 , Clarissa Araújo Gurgel Rocha  1   2   3 , Zaquer Suzana Munhoz Costa-Ferro  2   3 , Bruno Solano de Freitas Souza  1   2   3
Affiliations
Review

Modeling Autism Spectrum Disorders with Induced Pluripotent Stem Cell-Derived Brain Organoids

John Lenon de Souza Santos et al. Biomolecules. .

Abstract

Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders that affect communication and social interactions and present with restricted interests and repetitive behavior patterns. The susceptibility to ASD is strongly influenced by genetic/heritable factors; however, there is still a large gap in understanding the cellular and molecular mechanisms underlying the neurobiology of ASD. Significant progress has been made in identifying ASD risk genes and the possible convergent pathways regulated by these gene networks during development. The breakthrough of cellular reprogramming technology has allowed the generation of induced pluripotent stem cells (iPSCs) from individuals with syndromic and idiopathic ASD, providing patient-specific cell models for mechanistic studies. In the past decade, protocols for developing brain organoids from these cells have been established, leading to significant advances in the in vitro reproducibility of the early steps of human brain development. Here, we reviewed the most relevant literature regarding the application of brain organoids to the study of ASD, providing the current state of the art, and discussing the impact of such models on the field, limitations, and opportunities for future development.

Keywords: autism spectrum disorder; brain organoids; pluripotent stem cell.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the study design; collection, analyses, or interpretation of data; writing of the manuscript; or the decision to publish the results.

Figures

Figure 1
Figure 1
Cell reprogramming and 3D differentiation towards neural tissues. Somatic cells from the patient, such as fibroblasts and peripheral blood mononuclear cells (PBMC), undergo cellular reprogramming from the insertion of Yamanaka factors. These cells become induced pluripotent stem cells (iPSCs) and are used to generate 3D structures such as brain organoids and spheroids.
Figure 2
Figure 2
Applications of brain organoids in autism spectrum disorder (ASD) studies. Three-dimensional structures have been used in drug testing to evaluate the protein and gene profile of the cells from which they were generated; they have become an important tool in basic research and enabled the beginning of the emergence of personalized medicine.
See this image and copyright information in PMC

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