Combined therapeutic strategy using erythropoietin and mesenchymal stem cells potentiates neurogenesis after transient focal cerebral ischemia in rats.
J Cereb Blood Flow Metab. 2008-05-14; 28(9): 1552-1563
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1. J Cereb Blood Flow Metab. 2008 Sep;28(9):1552-63. doi: 10.1038/jcbfm.2008.40.
Epub 2008 May 14.
Combined therapeutic strategy using erythropoietin and mesenchymal stem cells
potentiates neurogenesis after transient focal cerebral ischemia in rats.
Esneault E(1), Pacary E, Eddi D, Freret T, Tixier E, Toutain J, Touzani O,
Schumann-Bard P, Petit E, Roussel S, Bernaudin M.
(1)Centre d’Imagerie-Neurosciences et Applications aux PathologieS (CI-NAPS), UMR
6232, Université de Caen Basse-Normandie, Université Paris Descartes, CNRS, CEA,
CERVOxy group, Hypoxia and Cerebrovascular Pathophysiology, Caen Cedex, France.
Many studies showed beneficial effects of either erythropoietin (EPO) or
mesenchymal stem cells (MSCs) treatment in cerebral ischemia. In addition to a
neuroprotective role, not only EPO but also MSC favors neurogenesis and
functional recovery. In an attempt to further improve postischemic tissue repair,
we investigated the effect of a systemic administration of MSC, in the presence
or not of EPO, on neurogenesis and functional recovery in a transient focal
cerebral ischemia model in the adult rat. Twenty-four hours after ischemia, the
rats were divided into four groups, namely vehicle, MSC, EPO, and MSC+EPO, and
received a single intravenous injection of MSC (2 x 10(6) cells) and/or a
repeated intraperitoneal administration of EPO (1,000 UI/kg) for 3 days. The
lesion volume, the MSC outcome, neurogenesis, and functional recovery were
assessed 51 days after ischemia. The results showed that cellular proliferation
and neurogenesis were increased along the lateral ventricle wall in the MSC+EPO
group, whereas no significant effect was observed in groups receiving MSC or EPO
alone. This effect was accompanied by an improvement of mnesic performances.
Mesenchymal stem cells expressing neuronal or glial markers were detected in the
ischemic hemisphere. These results suggest that EPO could act in a synergistic
way with MSC to potentiate the postischemic neurogenesis.
PMID: 18478023 [Indexed for MEDLINE]