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CXCL12-mediated guidance of migrating embryonic stem cell-derived neural progenitors transplanted into the hippocampus
- Source :
- PLoS ONE, PLoS ONE, Vol 5, Iss 12, p e15856 (2010)
- Publication Year :
- 2010
-
Abstract
- Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus can induce lesions in the dentate gyrus (DG) that lead to cell death within the upper blade. Using a mouse model of temporal lobe epilepsy, we previously observed that embryonic stem cell-derived neural progenitors (ESNPs) survive and differentiate within the granule cell layer after stereotaxic delivery to the DG, replacing the endogenous cells of the upper blade. To investigate the mechanisms for ESNP migration and repair in the DG, we examined the role of the chemokine CXCL12 in mice subjected to kainic acid-induced seizures. We now show that ESNPs transplanted into the DG show extensive migration through the upper blade, along the septotemporal axis of the hippocampus. Seizures upregulate CXCL12 and infusion of the CXCR4 antagonist AMD3100 by osmotic minipump attenuated ESNP migration. We also demonstrate that seizures promote the differentiation of transplanted ESNPs toward neuronal rather than astrocyte fates. These findings suggest that ESNPs transplanted into the adult rodent hippocampus migrate in response to cytokine-mediated signals.
- Subjects :
- Male
Mouse
Cell Survival
Cellular differentiation
Neurogenesis
Hippocampus
lcsh:Medicine
Cell Migration
Biology
Mice
Model Organisms
Neural Stem Cells
Developmental Neuroscience
Cell Movement
Seizures
Temporal Lobe Epilepsy
medicine
Morphogenesis
Animals
Progenitor cell
lcsh:Science
Embryonic Stem Cells
Neurons
Multidisciplinary
Epilepsy
Dentate gyrus
Stem Cells
lcsh:R
Cell Differentiation
Animal Models
Fibroblasts
Granule cell
Embryonic stem cell
Chemokine CXCL12
Cell biology
medicine.anatomical_structure
Epilepsy, Temporal Lobe
Neurology
Immunology
Dentate Gyrus
Medicine
lcsh:Q
Stem cell
Astrocyte
Research Article
Developmental Biology
Neuroscience
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....262654deca604a3ca2d531e0619a6da4