title: A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons.
abstract: The recent progress in stem cell techniques has broadened the horizon for in vitro disease modeling. For desired in vivo 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 in vivo 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 in vitro model has higher resemblance to the AD pathology than conventional 2D cultures and could be used in further studies of the disease.
authors.affiliation: Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mari
authors.initials: M
authors.lastname: Pekkanen-Mattila
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Shahsavani
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Falk
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Teixeira
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. Electronic address: anna.herland@ki.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Herland
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D054462:p21-Activated Kinases
keywords: 3D culture; Alzheimer's disease; Mechanotransduction; Neuron; Self-assembling peptide; iPSCs