期刊
TRENDS IN MOLECULAR MEDICINE
卷 24, 期 9, 页码 805-820出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2018.06.009
关键词
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资金
- Intramural Research Program of the National Institutes of Health at the National Institute of Neurological Disorders and Stroke
- National Center for Advancing Translational Sciences
- National Cancer Institute
- National Institute of Dental and Craniofacial Research
- Lieber Institute for Brain Development
Use of human pluripotent stem cells (hPSCs) and their differentiated derivatives have led to recent proof-of-principle drug discoveries, defining a pathway to the implementation of hPSC-based drug discovery (hPDD). Current hPDD strategies, however, have inevitable conceptual biases and technological limitations, including the dimensionality of cell-culture methods, cell maturity and functionality, experimental variability, and data reproducibility. In this review, we dissect representative hPDD systems via analysis of hPSC-based 2D-monolayers, 3D culture, and organoids. We discuss mechanisms of drug discovery and drug repurposing, and roles of membrane drug transporters in tissue maturation and hPDD using the example of drugs that target various mutations of CFTR, the cystic fibrosis transmembrane conductance regulator gene, in patients with cystic fibrosis.
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