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| Status |
Public on May 01, 2011 |
| Title |
Study the effect of mesenchymal stem cells on isolated cortical neurons |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Primary cortical neurons were isolated from E15 mice and after 6 days in vitro were untreated or treated for 24 h with mesenchymal stem cell conditioned medium. Neuron gene expression was profiled and compared between the two different conditions (neurons and neurons+MSC cm) to investigate the molecular mechanisms of MSC neuroprotection. Mesenchymal stem cells (MSC) promote functional recovery in experimental models of central nervous system (CNS) pathology and are currently being tested in clinical trials for stroke, multiple sclerosis and CNS injury. Their beneficial effects are attributed to the activation of endogenous CNS protection and repair processes as well as immune regulation but their mechanisms of action are poorly understood. Here we investigated the neuroprotective effects of mouse MSC in rodent MSC-neuron co-cultures and mice using models of glutamate excitotoxicity. A 24 hr pre-culture of mouse primary cortical neurons with MSC protected them against glutamate (NMDA) receptor-induced death and conditioned medium from MSC (MSC CM) was sufficient for this effect. Protection by MSC CM was associated with reduced mRNA levels of genes encoding NMDA receptor subunits, and increased levels for genes associated with non-neuronal and stem cell types, as shown by RT-PCR and cDNA microarray analyses. Changes in gene expression were not associated with alterations in cell lineage representation within the cultures. Further, MSC CM-mediated neuroprotection in rat retinal ganglion cells was associated with reduced glutamate-induced calcium influx. The adoptive transfer of EGFP+MSC in a mouse kainic acid epilepsy model also provided neuroprotection against glutamate excitotoxicity in vivo, as shown by reduced neuron damage and glial cell activation in the hippocampus. These results show that MSC mediate direct neuroprotection by reducing neuronal sensitivity to glutamate receptor ligands and altering gene expression, and suggest a link between the therapeutic effects of MSC and the activation of cell plasticity in the damaged CNS.
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| Overall design |
In vitro cultures primary cortical neurons from mice were protected from glutamate excitotoxicity when pre-treated with MSC cm. Global gene expression changes induced in neurons before and after treatment with MSC cm were investigated using a cDNA spotted macroarray filter. Two samples were analyzed in duplicate: neurons alone (untreated) and neurons+MSC cm.
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| Contributor(s) |
Probert L, Tseveleki V |
| Citation(s) |
22561409 |
| |
| Submission date |
Dec 22, 2010 |
| Last update date |
Jun 08, 2012 |
| Contact name |
Vivian Tseveleki |
| E-mail(s) |
vtseveleki@hotmail.com
|
| Phone |
+302106478863
|
| Fax |
+302106456547
|
| URL |
http://www.pasteur.gr/205/2074.aspx
|
| Organization name |
Hellenic Pasteur Institute
|
| Department |
Molecular Genetics
|
| Lab |
Molecular Genetics
|
| Street address |
127 Vasilissis Sophias Avenue
|
| City |
Athens |
| ZIP/Postal code |
11521 |
| Country |
Greece |
| |
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| Platforms (1) |
| GPL145 |
Atlas Mouse 1.2 Array II (Cat. #7857-1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA135149 |
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