Embryonic Stem Cell-Derived Neural Stem Cells Fuse with Microglia and Mature Neurons§

Authors

  • Carlo Cusulin,

    1. Laboratory of Stem Cells and Restorative Neurology Department of Laboratory Medicine, University Hospital, SE-22184 Lund, Sweden
    2. Lund Stem Cell Center, Lund, Sweden
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  • Emanuela Monni,

    1. Laboratory of Stem Cells and Restorative Neurology Department of Laboratory Medicine, University Hospital, SE-22184 Lund, Sweden
    2. Lund Stem Cell Center, Lund, Sweden
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  • Henrik Ahlenius,

    1. Laboratory of Stem Cells and Restorative Neurology Department of Laboratory Medicine, University Hospital, SE-22184 Lund, Sweden
    2. Lund Stem Cell Center, Lund, Sweden
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  • James Wood,

    1. Laboratory of Stem Cells and Restorative Neurology Department of Laboratory Medicine, University Hospital, SE-22184 Lund, Sweden
    2. Lund Stem Cell Center, Lund, Sweden
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  • Jan Claas Brune,

    1. Lund Stem Cell Center, Lund, Sweden
    2. Laboratory of Mesenchymal Stem Cells and Cellular Therapies, Department of Laboratory Medicine, University Hospital, SE-22184 Lund, Sweden
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  • Olle Lindvall,

    1. Laboratory of Stem Cells and Restorative Neurology Department of Laboratory Medicine, University Hospital, SE-22184 Lund, Sweden
    2. Lund Stem Cell Center, Lund, Sweden
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  • Zaal Kokaia

    Corresponding author
    1. Laboratory of Stem Cells and Restorative Neurology Department of Laboratory Medicine, University Hospital, SE-22184 Lund, Sweden
    2. Lund Stem Cell Center, Lund, Sweden
    • Lund Stem Cell Center, University Hospital BMC B10, SE-221 84 Lund, Sweden
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    • Telephone: +46 46 222 0276; Fax: +46 46 222 0560


  • Author contributions: C.C. and E.M.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing, H.A., J.W., and J.C.B.: collection and assembly of data and data analysis and interpretation; O.L. and Z.K.: conception and design, financial support, data analysis and interpretation, and manuscript writing. C.C. and E.M. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS November 7, 2012.

Abstract

Transplantation of neural stem cells (NSCs) is a novel strategy to restore function in the diseased brain, acting through multiple mechanisms, for example, neuronal replacement, neuroprotection, and modulation of inflammation. Whether transplanted NSCs can operate by fusing with microglial cells or mature neurons is largely unknown. Here, we have studied the interaction of a mouse embryonic stem cell-derived neural stem (NS) cell line with rat and mouse microglia and neurons in vitro and in vivo. We show that NS cells spontaneously fuse with cocultured cortical neurons, and that this process requires the presence of microglia. Our in vitro data indicate that the NS cells can first fuse with microglia and then with neurons. The fused NS/microglial cells express markers and retain genetic and functional characteristics of both parental cell types, being able to respond to microglia-specific stimuli (LPS and IL-4/IL-13) and to differentiate to neurons and astrocytes. The NS cells fuse with microglia, at least partly, through interaction between phosphatidylserine exposed on the surface of NS cells and CD36 receptor on microglia. Transplantation of NS cells into rodent cortex results in fusion with mature pyramidal neurons, which often carry two nuclei, a process probably mediated by microglia. The fusogenic role of microglia could be even more important after NSC transplantation into brains affected by neurodegenerative diseases associated with microglia activation. It remains to be elucidated how the occurrence of the fused cells will influence the functional outcome after NSC transplantation in the diseased brain. STEM CELLS 2012;30:2657–2611

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