Maman M, Goldman O, Cohen Solal T, Laifenfeld D. Induced pluripotent stem cell-derived neuronal models in psychiatry: Mechanistic insights and translational horizons. World J Stem Cells 2026; 18(9): 124169 [DOI: 10.4252/wjsc.124169]
Corresponding Author of This Article
Moria Maman, PhD, Research and Development, NeuroKaire, Yigal Alon 126, Tel Aviv-Yafo 6744332, Tel Aviv, Israel. moria@neurokaire.com
Research Domain of This Article
Neurosciences
Article-Type of This Article
review-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Moria Maman, Research and Development, NeuroKaire, Tel Aviv-Yafo 6744332, Tel Aviv, Israel
Orit Goldman, Talia Cohen Solal, Daphna Laifenfeld, NeuroKaire, Tel Aviv-Yafo 6744332, Tel Aviv, Israel
Author contributions: Maman M conceived the review, performed the literature search, analyzed and interpreted the literature, prepared the figure and table, and wrote the original manuscript; Goldman O, Cohen Solal T, and Laifenfeld D critically revised the manuscript for important intellectual content and contributed to the interpretation of the literature. All authors reviewed, approved the final version of the manuscript, and agree to be accountable for all aspects of the work.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Moria Maman, PhD, Research and Development, NeuroKaire, Yigal Alon 126, Tel Aviv-Yafo 6744332, Tel Aviv, Israel. moria@neurokaire.com
Received: June 9, 2026 Revised: July 13, 2026 Accepted: August 26, 2026 Published online: September 26, 2026 Processing time: 108 Days and 13.9 Hours
Abstract
Human induced pluripotent stem cell (iPSC)-derived neuronal models have become an important platform for investigating psychiatric disorders by enabling experimental access to human neurons carrying patient-specific genetic risk. Advances in reprogramming, neural differentiation, single-cell profiling, electrophysiology, and genome editing have facilitated the accessibility of knowledge which was once unavailable. Psychiatric disorders pose particular challenges for in vitro modeling due to their polygenic architecture, developmental origins, and clinical heterogeneity. This review summarizes the current state of iPSC-derived neuronal technologies, summarizes key findings across major psychiatric disorders, and discusses methodological limitations and emerging translational directions. We emphasize quantitative functional phenotyping and patient stratification as central principles for future progress in precision psychiatry. The future of precision psychiatry relies on two central principles; analyzing patient specific neuronal characteristics with an objective, comparable readout, and classifying patients into biologically meaningful subgroups which share common features such as mechanism, biomarker profile, or functional and structural signature.
Core Tip: Human induced pluripotent stem cell-derived neuronal models are transforming psychiatric research by enabling direct investigation of patient-specific neural phenotypes in a human genetic context. Beyond disease modeling, emerging evidence suggests that quantitative functional phenotyping can identify biologically meaningful patient subgroups and treatment-response signatures. This review synthesizes findings across major psychiatric disorders and proposes a conceptual shift from reproducing diagnostic categories in vitro toward mechanism-based stratification. Such approaches may bridge the gap between psychiatric genetics and clinical decision-making, advancing the development of precision psychiatry.
