The Intracerebroventricular Injection of Murine Mesenchymal Stromal Cells Engineered to Secrete Epidermal Growth Factor Does Not Prevent Loss of Neurogenesis in Irradiated Mice
| Autor: | Kerstin Killer, Oanh Le, Christian Beauséjour |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Genetically modified mouse
Recombinant Epidermal Growth Factor Doublecortin Protein Neurogenesis Genetic Vectors Biophysics Subventricular zone Radiation-Protective Agents Mesenchymal Stem Cell Transplantation Mice Epidermal growth factor Transduction Genetic medicine Animals Radiology Nuclear Medicine and imaging Injections Intraventricular Radiation biology Epidermal Growth Factor Mesenchymal stem cell Lentivirus Mesenchymal Stem Cells Recombinant Proteins Doublecortin Cell biology Mice Inbred C57BL medicine.anatomical_structure nervous system Apoptosis biology.protein Female Cranial Irradiation |
| Zdroj: | Radiation research. 196(3) |
| ISSN: | 1938-5404 |
| Popis: | Decreased neurogenesis after brain exposure to ionizing radiation is linked to neurocognitive impairments. Using transgenic mouse models, we previously showed that abrogation of radiation-induced senescence, or apoptosis, can partially rescue neurogenesis in the subventricular and hippocampus regions. Here, we evaluate whether the injection of recombinant epidermal growth factor (rEGF) or mesenchymal stromal cells (MSC) engineered to secrete EGF (MSC-EGF) can preserve neurogenesis. Using doublecortin (Dcx) expression and BrdU incorporation assays, we found that the injection of rEGF into the subventricular zone (SVZ) promotes neurogenesis, despite increasing apoptosis, in the brain of irradiated mice. The effect of rEGF was mostly localized, as Dcx expression was not induced in the hippocampus region and limited in the contralateral SVZ. Surprisingly, the injection of bone marrow-derived MSC alone, or secreting EGF, did not result in increased neurogenesis despite the fact that part of the MSC survived a few weeks after injection. Our results suggest that only a supraphysiological concentration of rEGF can promote neurogenesis, likely through a direct mitogenic effect. |
| Databáze: | OpenAIRE |
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