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• W3167817900 abstract "Induced pluripotent stem cells (iPSCs) can be differentiated into virtually every desired cell type, offering significant potential for modeling human diseases in vitro . A disadvantage is that iPSC-derived cells represent an immature, which presents a major limitation for modeling age-related diseases such as Alzheimer’s disease. Evidence suggests that culturing iPSC neurons in a 3D environment may increase neuronal maturity. However, current 3D cell culture systems are cumbersome and time-consuming. We cultured iPSC-derived excitatory neurons in 3D precast hydrogel plates and compared their maturation to 2D monolayer cultures. In contrast to other hydrogel-based 3D culture techniques, which require full encapsulation of cells, our hydrogel allows the seeded iPSCs and iPSC neurons to simply infiltrate the gel. IPSC-neurons grew to a depth of 500 µm into the hydrogel. Cell viability was comparable to 2D cultures over the course of three weeks, with even better neuronal survival in 3D cultures at the one-week time point. Levels of neuronal and synaptic maturation markers, namely, neural cell adhesion molecule 1 (NCAM1) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR2, were strongly increased in 3D cultures. Furthermore, we identified 4-repeat (4R) tau in 3D cultures, which was not detectable in 2D cultures. We describe a simple, hydrogel-based method for 3D iPSC culture that can serve as a fast and drug-screening-compatible platform to identify new mechanisms and therapeutic targets for brain diseases. We further provided evidence for the increased maturation of iPSC neurons in a 3D microenvironment. • Precast PEG-based hydrogels with density gradients enable sequential seeding of iPSCs/iN cells and glial cells. • Neurons grow to a depth of 500 µm into the hydrogel. • iPS-derived neurons show increased maturation in 3D hydrogels. • The 4-repeat form of tau is detectable after 3 weeks in 3D cultures, but not in 2D cultures." @default.
• W3167817900 created "2021-06-22" @default.
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• W3167817900 date "2021-08-01" @default.
• W3167817900 modified "2023-09-24" @default.
• W3167817900 title "Increased maturation of iPSC-derived neurons in a hydrogel-based 3D culture" @default.
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• W3167817900 doi "https://doi.org/10.1016/j.jneumeth.2021.109254" @default.
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