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Engineering human pluripotent stem cell-derived 3D brain tissues for drug discovery

Journal of Translational Neuroscience 2016年第2期1卷 38-48页

作者： Ha Nam Nguyen HongjunSong Guoli Ming Institute for cell Engineering Johns Hopkins University School of MedicineBaltimoreMD21205USA Department of Neurology Johns Hopkins University School of MedicineBaltimoreMD21205USA The Solomon H Snyder Department of Neuroscience Johns Hopkins University School of MedicineBaltimoreMD21205USA Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of MedicineBaltimoreMD21205USA

The quest to find novel therapeutics for mental and neurological disorders has been hindered by the lack of access to l ive human brain samples and relevant experimental models. Conventional 2D human pluripotent stem cell-derived neuronal cultures and animal models do not ful ly recapitulate many endogenous human biochemical processes and disease phenotypes. Currently, the majority of candidate drugs obtained from preclinical testing in conventional systems does not usually translate into success and have a high failure rate in clinical trials. Recent advancements in bioengineering and stem cell technologies have resulted in three-dimensional brain-like tissues, such as oragnoids, which better resemble endogenous tissue and are more physiologically relevant than monolayer cultures. These brain-like tissues can bridge the gap between existing models and the patient, and may revolutionize the field of translational neuroscience. Here, we discuss utilities and challenges of using stem cell-derived human brain tissues in basic research and pharmacotherapy.

关键词： stem cell-derived brain tissues three-dimensional (3D) translational neuroscience brain organoids

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