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Generation of human iPSC-derived neural progenitor cells (NPCs) as drug discovery model for neurological and mitochondrial disorders

Item Type:Article
Title:Generation of human iPSC-derived neural progenitor cells (NPCs) as drug discovery model for neurological and mitochondrial disorders
Creators Name:Zink, A. and Lisowski, P. and Prigione, A.
Abstract:The high attrition rate in drug development processes calls for additional human-based model systems. However, in the context of brain disorders, sampling live neuronal cells for compound testing is not applicable. The use of human induced pluripotent stem cells (iPSCs) has revolutionized the field of neuronal disease modeling and drug discovery. Thanks to the development of iPSC-based neuronal differentiation protocols, including tridimensional cerebral organoids, it is now possible to molecularly dissect human neuronal development and human brain disease pathogenesis in a dish. These approaches may allow dissecting patient-specific treatment efficacy in a disease-relevant cellular context. For drug discovery approaches, however, a highly reproducible and cost-effective cell model is desirable. Here, we describe a step-by-step process for generating robust and expandable neural progenitor cells (NPCs) from human iPSCs. NPCs generated with this protocol are homogeneous and highly proliferative. These features make NPCs suitable for the development of high-throughput compound screenings for drug discovery. Human iPSC-derived NPCs show a metabolism dependent on mitochondrial activity and can therefore be used also to investigate neurological disorders in which mitochondrial function is affected. The protocol covers all steps necessary for the preparation, culture, and characterization of human iPSC-derived NPCs. Graphic abstract: Schematic of the protocol for the generation of human iPSC-derived NPCs.
Keywords:Human iPSCs, Neural Progenitor Cells, Drug Discovery, Stem Cell Differentiation, Neuronal Disease Modeling, Mitochondrial Disorders
Publisher:Bio-protocol LLC
Page Range:e3939
Date:5 March 2021
Additional Information:Copyright © 2021 The Authors; exclusive licensee Bio-protocol LLC.
Official Publication:https://doi.org/10.21769/BioProtoc.3939
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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