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

Cusulin, Carlo; Monni, Emanuela LU ; Ahlenius, Henrik LU ; Wood, James LU ; Brune, Jan Claas; Lindvall, Olle LU and Kokaia, Zaal LU (2012) In Stem Cells
Abstract
Transplantation of neural stem cells (NSCs) is a novel strategy to restore function in the diseased brain, acting through multiple mechanisms, e.g., 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 co-cultured 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... (More)
Transplantation of neural stem cells (NSCs) is a novel strategy to restore function in the diseased brain, acting through multiple mechanisms, e.g., 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 co-cultured 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 (PS) 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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Stem Cells
publisher
AlphaMed Press
external identifiers
  • WOS:000311493600006
  • PMID:22961761
  • Scopus:84870334957
ISSN
1549-4918
DOI
10.1002/stem.1227
language
English
LU publication?
yes
id
cf5fb693-b6e0-4d63-a356-e434db71738b (old id 3124087)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22961761?dopt=Abstract
date added to LUP
2012-10-04 17:29:15
date last changed
2016-11-01 10:22:41
@misc{cf5fb693-b6e0-4d63-a356-e434db71738b,
  abstract     = {Transplantation of neural stem cells (NSCs) is a novel strategy to restore function in the diseased brain, acting through multiple mechanisms, e.g., 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 co-cultured 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 (PS) 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.},
  author       = {Cusulin, Carlo and Monni, Emanuela and Ahlenius, Henrik and Wood, James and Brune, Jan Claas and Lindvall, Olle and Kokaia, Zaal},
  issn         = {1549-4918},
  language     = {eng},
  month        = {09},
  publisher    = {ARRAY(0x986cf08)},
  series       = {Stem Cells},
  title        = {Embryonic Stem Cell-Derived Neural Stem Cells Fuse with Microglia and Mature Neurons.},
  url          = {http://dx.doi.org/10.1002/stem.1227},
  year         = {2012},
}