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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 27 NOV 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 12, pages 2657–2671, December 2012
How to Cite
Cusulin, C., Monni, E., Ahlenius, H., Wood, J., Brune, J. C., Lindvall, O. and Kokaia, Z. (2012), Embryonic Stem Cell-Derived Neural Stem Cells Fuse with Microglia and Mature Neurons. STEM CELLS, 30: 2657–2671. doi: 10.1002/stem.1227
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.
- Issue published online: 27 NOV 2012
- Article first published online: 27 NOV 2012
- Accepted manuscript online: 7 SEP 2012 01:05PM EST
- Manuscript Accepted: 10 AUG 2012
- Manuscript Received: 22 FEB 2012
- Swedish Research Council, European Union projects StemStroke. Grant Number: (037526)
- TargetBraIn. Grant Number: (279017)
- AFA Foundation, and Swedish Government Initiative for Strategic Research Areas (StemTherapy)
- Neural stem cells;
- Cell fusion;
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