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Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-ß plaques.
Preman, Pranav; Tcw, Julia; Calafate, Sara; Snellinx, An; Alfonso-Triguero, Maria; Corthout, Nikky; Munck, Sebastian; Thal, Dietmar Rudolf; Goate, Alison M; De Strooper, Bart; Arranz, Amaia M.
Afiliação
  • Preman P; VIB Center for Brain & Disease Research, Leuven, Belgium.
  • Tcw J; Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium.
  • Calafate S; Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Snellinx A; Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Alfonso-Triguero M; Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Corthout N; VIB Center for Brain & Disease Research, Leuven, Belgium.
  • Munck S; Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium.
  • Thal DR; VIB Center for Brain & Disease Research, Leuven, Belgium.
  • Goate AM; Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium.
  • De Strooper B; Achucarro Basque Center for Neuroscience, Leioa, Spain.
  • Arranz AM; Department of Neurosciences, Universidad del País Vasco (UPV/EHU), Leioa, Spain.
Mol Neurodegener ; 16(1): 68, 2021 09 25.
Article em En | MEDLINE | ID: mdl-34563212
BACKGROUND: Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer's disease comes from molecular and functional studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression. RESULTS: To address these challenges, we established an approach to study human astrocytes within the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains. Xenografted hiPSC-derived astrocyte progenitors differentiated into astrocytes that integrated functionally within the mouse host brain and matured in a cell-autonomous way retaining human-specific morphologies, unique features, and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes responded to the presence of amyloid plaques undergoing morphological changes that seemed independent of the APOE allelic background. CONCLUSIONS: In sum, we describe here a promising approach that consist of transplanting patient-derived and genetically modified astrocytes into the mouse brain to study human astrocyte pathophysiology in the context of Alzheimer´s disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes Induzidas / Doença de Alzheimer Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes Induzidas / Doença de Alzheimer Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article