title: Induced Pluripotent Stem Cell Models to Enable In Vitro Models for Screening in the Central Nervous System.
abstract: There is great need to develop more predictive drug discovery tools to identify new therapies to treat diseases of the central nervous system (CNS). Current nonpluripotent stem cell-based models often utilize non-CNS immortalized cell lines and do not enable the development of personalized models of disease. In this review, we discuss why in vitro models are necessary for translational research and outline the unique advantages of induced pluripotent stem cell (iPSC)-based models over those of current systems. We suggest that iPSC-based models can be patient specific and isogenic lines can be differentiated into many neural cell types for detailed comparisons. iPSC-derived cells can be combined to form small organoids, or large panels of lines can be developed that enable new forms of analysis. iPSC and embryonic stem cell-derived cells can be readily engineered to develop reporters for lineage studies or mechanism of action experiments further extending the utility of iPSC-based systems. We conclude by describing novel technologies that include strategies for the development of diversity panels, novel genomic engineering tools, new three-dimensional organoid systems, and modified high-content screens that may bring toxicology into the 21st century. The strategic integration of these technologies with the advantages of iPSC-derived cell technology, we believe, will be a paradigm shift for toxicology and drug discovery efforts.
authors: 1 Wake Forest Institute for Regenerative Medicine , Winston-Salem, North Carolina.
authors: Joshua G
authors: JG
authors: Hunsberger
authors: 2 Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors: Anastasia G
authors: AG
authors: Efthymiou
authors: 3 National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH) , Bethesda, Maryland.
authors: Nasir
authors: N
authors: Malik
authors: 4 National Toxicology Program, National Institute of Environmental Health Sciences , Research Triangle Park, North Carolina.
authors: Mamta
authors: M
authors: Behl
authors: 1 Wake Forest Institute for Regenerative Medicine , Winston-Salem, North Carolina.
authors: Ivy L
authors: IL
authors: Mead
authors: 5 Buck Institute for Age Research , Novato, California.
authors: Xianmin
authors: X
authors: Zeng
authors: 6 National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) , Rockville, Maryland.
authors: Anton
authors: A
authors: Simeonov
authors: 7 New York Stem Cell Foundation , New York, New York.
authors: Mahendra
authors: M
authors: Rao
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*
chemical_list: D002491:Central Nervous System Agents