3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders

Journal of Biomedical Science

Review

Raphael M. Bendriem¹  Rong-Fong Shen²  Wells W. Wu²  Chun-Ting Lee³ 

[1] Center for Neurogenetics, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 10021, New York, NY, USA;Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, FDA, 20993, Silver Spring, MD, USA;Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, FDA, 20993, Silver Spring, MD, USA;Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Building 52, Rm 1121, 10903 New Hampshire Avenue, 20993, Silver Spring, MD, USA;

关键词: 3D brain organoids;    Induced pluripotent stem cells;    Brain development;    Neocortex;    Neurodevelopmental disorder;    Neurodegenerative disorder;    Microcephaly;    Drugs;    Autism;    Alzheimer’s disease;   

DOI  :  10.1186/s12929-017-0362-8

 received in 2017-06-23, accepted in 2017-08-09,  发布年份 2017

来源: Springer

【 摘 要 】

Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain’s 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials. Studies using patient-derived brain organoids have already revealed novel insights into molecular and genetic mechanisms of certain complex human neurological disorders such as microcephaly, autism, and Alzheimer’s disease. Furthermore, the combination of hiPSC technology and small-molecule high-throughput screening (HTS) facilitates the development of novel pharmacotherapeutic strategies, while transcriptome sequencing enables the transcriptional profiling of patient-derived brain organoids. Finally, the addition of CRISPR/Cas9 genome editing provides incredible potential for personalized cell replacement therapy with genetically corrected hiPSCs. This review describes the history and current state of 3D brain organoid differentiation strategies, a survey of applications of organoids towards studies of neurodevelopmental and neurodegenerative disorders, and the challenges associated with their use as in vitro models of neurological disorders.

【 授权许可】

CC BY   
© The Author(s). 2017