Brain organoids: building higher-order complexity and neural circuitry models

Gulimiheranmu Maisumu; Stephanie Willerth; Michael Nestor; Ben Waldau; Stefan Schülke; Francesco V Nardi; Osama Ahmed; You Zhou; Madel Durens; Bo Liang; Abraam M Yakoub

doi:10.1016/j.tibtech.2025.02.009

Brain organoids: building higher-order complexity and neural circuitry models

Trends Biotechnol. 2025 Apr 11:S0167-7799(25)00046-0. doi: 10.1016/j.tibtech.2025.02.009. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA; Department of Biomedical Engineering, University of North Dakota, Grand Forks, ND, USA.
² Department of Biomedical Engineering, University of Victoria, Victoria, BC, Canada.
³ National Academies of Sciences, Engineering, and Medicine, Washington, DC, USA.
⁴ Department of Neurological Surgery, University of California Davis, Sacramento, CA, USA.
⁵ Molecular Allergology, Paul-Ehrlich-Institut, Langen, Germany; Research Allergology (ALG 5), Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
⁶ Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA.
⁷ Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸ Department of Biomedical Engineering, University of North Dakota, Grand Forks, ND, USA.
⁹ Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA. Electronic address: ayakoub@bwh.harvard.edu.

PMID: 40221251
DOI: 10.1016/j.tibtech.2025.02.009

Abstract

Brain organoids are 3D tissue models of the human brain that are derived from pluripotent stem cells (PSCs). They have enabled studies that were previously stymied by the inaccessibility of human brain tissue or the limitations of mouse models of some brain diseases. Despite their enormous potential, brain organoids have had significant limitations that prevented them from recapitulating the full complexity of the human brain and reduced their utility in disease studies. We describe recent progress in addressing these limitations, especially building complex organoids that recapitulate the interactions between multiple brain regions, and reconstructing in vitro the neural circuitry present in in vivo. These major advances in the human brain organoid technology will remarkably facilitate brain disease modeling and neuroscience research.

Keywords: assembloids; brain development; brain disease; brain organoids; neural circuitry.

Publication types

Review