Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (10): 4495-4505.doi: 10.4103/NRR.NRR-D-25-01004

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Stem cell derived neural organoids approaches for neurological diseases

Rosalie Elvira1, #, Xiao-Xue Dong2, #, Alfred Sun Xuyang3, Wai Hon Chooi3, Huck Hui Ng4, Hongyan Wang3, Yun-Cheng Wu2, *, Eng King Tan1, 3, 5, *, Zhi Dong Zhou1, 3, *   

  1. 1National Neuroscience Institute of Singapore, Singapore; 
    2Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 
    3Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore; 
    4Genome Institute of Singapore, Singapore; 
    5Department of Neurology, Singapore General Hospital, Singapore
  • Online:2026-10-15 Published:2026-06-11
  • Supported by:
    This work was supported by the Open Fund Large Collaborative Grant (MOH‑OFLCG24may‑0004) and the Singapore Translational Research (STaR) Investigator Award (NMRC/STaR/0030/2018) awarded to Dr. EKT; the Open und‑Individual Research Grant (OF‑IRG, MOH‑001506), Clinician Scientist‑Individual Research Grants (CS‑IRG) (MOH‑001091, CIRG23jul‑0006), HLCA2024 (HLCA24Mar‑0019), and SingHealth‑Duke‑NUS Academic Medicine Position Grant awarded to Dr. ZDZ; and the National Natural Science Foundation of China (82171243) awarded to Dr. YCW.

Abstract: Traditional two-dimensional cultures and animal models often fall short in capturing the complexities of neurodevelopmental and neurodegenerative diseases. However, recently developed neural organoid approaches, three-dimensional structures derived from human pluripotent stem cells, have become powerful tools for modeling human neuronal development and disease. Unlike traditional models, neural organoids provide significant insights and improved modeling capabilities. Here, we explore various types of neural organoids in disease modeling and outline distinct protocols for generating each type, including specific patterning methods, growth factors, and differentiation durations. The potential and advantages of co-culturing neural organoids with other cells and tissues are also discussed. While neural organoids have already made significant contributions to neuroscience research, future directions should focus on enhancing their maturation and functionality. The progression of neural organoids approaches will generate more accurate and comprehensive disease models, ultimately adding to our understanding of disease pathogenesis and paving the way for future precision therapies for neurological diseases.

Key words: neural differentiation, neural organoids, neurogenesis, neurological diseases, stem cells, threedimensional models