The Intracerebroventricular Injection of Murine Mesenchymal Stromal Cells Engineered to Secrete Epidermal Growth Factor Does Not Prevent Loss of Neurogenesis in Irradiated Mice.
Radiat Res
; 196(3): 315-322, 2021 09 01.
Article
de En
| MEDLINE
| ID: mdl-34107047
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Radioprotecteurs
/
Transplantation de cellules souches mésenchymateuses
/
Facteur de croissance épidermique
/
Neurogenèse
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Radiat Res
Année:
2021
Type de document:
Article