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• W2881279370 endingPage "820" @default.
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• W2881279370 abstract "Human pluripotent stem cells (hPSCs) and their differentiated derivatives represent valuable cell resources for organogenesis, disease modeling, and hPSC-based drug discovery (hPDD) in vitro. Abundant contributing variables, including the dimensionality of cell-culture methods, cell maturity and functionality, and experimental variability, epitomize the major challenges of hPDD research. Targeting various CFTR mutations in organoids derived from patients with cystic fibrosis provides a proof-of-principle drug discovery model, defining a potential pathway to the implementation of hPDD for personalized medicine. 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. 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. in vitro cell culture conditions that combine coculture elements with a 3D environment. a microscale version of conventional bioreactors (macro-bioreactors), including microfluidic bioreactors, biochips, and cell-chip, which integrate numerous monitoring features used by macro-bioreactors. a process by which a cell, tissue, organ, or organism acquires its architectural characteristics. Morphogenesis is induced and controlled by many cellular and developmental programs. refers to naïve and primed pluripotent states established in the preimplantation embryos and the post-implantation epiblast, respectively, during embryogenesis. This distinct pluripotency also extends to pluripotent stem cells that have identical pluripotent features under cell culture conditions. a process by which an organism develops and produces its body parts of specific tissue structures and functions (e.g., the liver and the limb) during development. a stem cell-derived 3D multicellular miniature of physiologically relevant tissues in a culture dish, in which only stem cells are capable of self-renewal, self-organization, and differentiation toward adult tissues under corresponding conditions. compared with 4D-organoids, 5D-organoids have 1D-higher complexity, which is regulated by providing additional extrinsic signaling factors in 4D-organoids to generate highly physiologically relevant organoids. distinct types of cell clusters that incorporate into a preexisting cell group or host tissues to integrate their cellular effects." @default.
• W2881279370 created "2018-07-19" @default.
• W2881279370 creator A5025882946 @default.
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• W2881279370 date "2018-09-01" @default.
• W2881279370 modified "2023-10-03" @default.
• W2881279370 title "Pluripotent Stem Cell Platforms for Drug Discovery" @default.
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