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A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons

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Details

Original languageEnglish
Pages (from-to)1420-1428
Number of pages9
JournalBiomaterials
Volume35
Issue number5
DOIs
Publication statusPublished - Feb 2014
Publication typeA1 Journal article-refereed

Abstract

The recent progress in stem cell techniques has broadened the horizon for invitro disease modeling. For desired invivo like phenotypes, not only correct cell type specification will be critical, the microenvironmental context will be essential to achieve relevant responses. We demonstrate how a three dimensional (3D) culture of stem cell derived neurons can induce invivo like responses related to Alzheimer's disease, not recapitulated with conventional 2D cultures. To acquire a neural population of cells we differentiated neurons from neuroepithelial stem cells, derived from induced pluripotent stem cells. p21-activated kinase mediated sensing of Aβ oligomers was only possible in the 3D environment. Further, the 3D phenotype showed clear effects on F-actin associated proteins, connected to the disease processes. We propose that the 3D invitro model has higher resemblance to the AD pathology than conventional 2D cultures and could be used in further studies of the disease.

Keywords

  • 3D culture, Alzheimer's disease, IPSCs, Mechanotransduction, Neuron, Self-assembling peptide