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Publication : Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-? plaques.

First Author  Preman P Year  2021
Journal  Mol Neurodegener Volume  16
Issue  1 Pages  68
PubMed ID  34563212 Mgi Jnum  J:367316
Mgi Id  MGI:6766274 Doi  10.1186/s13024-021-00487-8
Citation  Preman P, et al. (2021) Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-beta plaques. Mol Neurodegener 16(1):68
abstractText  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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