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

Zhang, Dawei ; Pekkanen-Mattila, Mari ; Shahsavani, Mansoureh ; Falk, Anna LU ; Teixeira, Ana I and Herland, Anna (2014) In Biomaterials 35(5). p.8-1420
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... (More)

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.

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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer Disease/enzymology, Amyloid beta-Peptides/metabolism, Cell Differentiation, Cells, Cultured, Fluorescent Antibody Technique, Humans, Induced Pluripotent Stem Cells/cytology, Models, Biological, Neurons/cytology, Real-Time Polymerase Chain Reaction, p21-Activated Kinases/metabolism
in
Biomaterials
volume
35
issue
5
pages
9 pages
publisher
Elsevier
external identifiers
  • pmid:24290439
  • scopus:84890173885
ISSN
1878-5905
DOI
10.1016/j.biomaterials.2013.11.028
language
English
LU publication?
no
id
e2452b20-74df-4b32-a2c1-77d06c5058fb
date added to LUP
2021-08-10 13:18:17
date last changed
2024-04-20 09:39:54
@article{e2452b20-74df-4b32-a2c1-77d06c5058fb,
  abstract     = {{<p>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.</p>}},
  author       = {{Zhang, Dawei and Pekkanen-Mattila, Mari and Shahsavani, Mansoureh and Falk, Anna and Teixeira, Ana I and Herland, Anna}},
  issn         = {{1878-5905}},
  keywords     = {{Alzheimer Disease/enzymology; Amyloid beta-Peptides/metabolism; Cell Differentiation; Cells, Cultured; Fluorescent Antibody Technique; Humans; Induced Pluripotent Stem Cells/cytology; Models, Biological; Neurons/cytology; Real-Time Polymerase Chain Reaction; p21-Activated Kinases/metabolism}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{8--1420}},
  publisher    = {{Elsevier}},
  series       = {{Biomaterials}},
  title        = {{A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons}},
  url          = {{https://lup.lub.lu.se/search/files/101076475/A_3D_Alzheimer_s_disease_culture_model.pdf}},
  doi          = {{10.1016/j.biomaterials.2013.11.028}},
  volume       = {{35}},
  year         = {{2014}},
}