3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders
Autor: | Wells W. Wu, Chun-Ting Lee, Rong-Fong Shen, Raphael M Bendriem |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Endocrinology Diabetes and Metabolism Autism Clinical Biochemistry lcsh:Medicine Neocortex Review Biology 03 medical and health sciences Neurodevelopmental disorder Genome editing 3D brain organoids Organoid medicine CRISPR Animals Humans Pharmacology (medical) Induced pluripotent stem cell Molecular Biology Biochemistry (medical) lcsh:R Drugs Brain Cell Differentiation Neurodegenerative Diseases Cell Biology General Medicine Human brain Neurodegenerative disorder medicine.disease Embryonic stem cell Brain development Organoids Disease Models Animal Induced pluripotent stem cells 030104 developmental biology medicine.anatomical_structure Neurodevelopmental Disorders Microcephaly Neuroscience Reprogramming Alzheimer’s disease |
Zdroj: | Journal of Biomedical Science, Vol 24, Iss 1, Pp 1-12 (2017) Journal of Biomedical Science |
ISSN: | 1423-0127 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |