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Glia. 2015 Aug;63(8):1483-93. doi: 10.1002/glia.22862. Epub 2015 May 24.

Modeling cognition and disease using human glial chimeric mice.

Author information

1
Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York.
2
Center for Basic and Translational Neuroscience, University of Copenhagen Faculty of Medicine, Copenhagen, Denmark.

Abstract

As new methods for producing and isolating human glial progenitor cells (hGPCs) have been developed, the disorders of myelin have become especially compelling targets for cell-based therapy. Yet as animal modeling of glial progenitor cell-based therapies has progressed, it has become clear that transplanted hGPCs not only engraft and expand within murine hosts, but dynamically outcompete the resident progenitors so as to ultimately dominate the host brain. The engrafted human progenitor cells proceed to generate parenchymal astrocytes, and when faced with a hypomyelinated environment, oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human neurological and neuropsychiatric disease.

KEYWORDS:

cell transplant; glial progenitor; mouse models; neural stem cell; oligodendrocytic progenitor

PMID:
26010831
PMCID:
PMC4527525
DOI:
10.1002/glia.22862
[Indexed for MEDLINE]
Free PMC Article

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