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. 2024 Oct 8:18:1480845.
doi: 10.3389/fncel.2024.1480845. eCollection 2024.

Organoid intelligence for developmental neurotoxicity testing

Dowlette-Mary Alam El Din  1 , Jeongwon Shin  2 , Alexandra Lysinger  1 , Matthew J Roos  3 , Erik C Johnson  3 , Timothy J Shafer  4 , Thomas Hartung  1   5   6 , Lena Smirnova  1
Affiliations

Organoid intelligence for developmental neurotoxicity testing

Dowlette-Mary Alam El Din et al. Front Cell Neurosci. .

Abstract

The increasing prevalence of neurodevelopmental disorders has highlighted the need for improved testing methods to determine developmental neurotoxicity (DNT) hazard for thousands of chemicals. This paper proposes the integration of organoid intelligence (OI); leveraging brain organoids to study neuroplasticity in vitro, into the DNT testing paradigm. OI brings a new approach to measure the impacts of xenobiotics on plasticity mechanisms - a critical biological process that is not adequately covered in current DNT in vitro assays. Finally, the integration of artificial intelligence (AI) techniques will further facilitate the analysis of complex brain organoid data to study these plasticity mechanisms.

Keywords: artificial intelligence; developmental neurotoxicity; machine learning; organoid; organoid intelligence; synaptic plasiticity.

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Conflict of interest statement

Thomas Hartung is named inventor on a patent by Johns Hopkins University on the production of organoids, which is licensed to Axo-Sim, New Orleans, LA, USA. Thomas Hartung and Lena Smirnova are consultants for AxoSim, New Orleans, and Thomas Hartung is also a consultant for AstraZeneca and American Type Culture Collection (ATCC) on advanced cell culture methods. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Outline of organoid intelligence for developmental neurotoxicity testing. Using brain organoids interfacing with tools such as high-density microelectrode arrays (HD-MEAs) and optogenetic probes, electrophysiological data can be used to inform how xenobiotics impact the molecular mechanisms associated with cognition and modulate synaptic plasticity. Created in BioRender. Alam el din, D. (2024) BioRender.com/g91a488 (this is the publication license).
Figure 2
Figure 2
Envisioned use of OI for in vitro assessment assays for brain organoids. (A) An open-loop experiment, mimicking sensory processing, where task feedback is not used to stimulate the organoid. (B) A closed-loop experiment, mimicking reinforcement learning or behavioral tasks. (C) Potential assays which can be derived from brain organoid physiological data collected during open- and closed-loop experiments.
See this image and copyright information in PMC

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