- 作者: Chun-Ting Lee, Raphael M. Bendriem, Wells W. Wu and Rong-Fong Shen
- 作者服務機構: 1. Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, FDA, Silver Spring, MD 20993, USA 2. Center for Neurogenetics, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 E 61st St New York, NY 10065, USA 3. Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Building 52, Rm 1121, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA
- 中文摘要:
- 英文摘要:
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. - 中文關鍵字:
- 英文關鍵字: 3D brain organoids, Induced pluripotent stem cells, Brain development, Neocortex, Neurodevelopmental disorder, Neurodegenerative disorder, Microcephaly, Drugs, Autism, Alzheimer’s disease