Attractive therapeutic strategies to enhance post-
stroke recovery of aged brains include methods of cellular
therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since
stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of
cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an
autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived
therapy includes the grafting of stem cells as well as the delayed induction of endogenous
stem cell mobilization and homing by the stem cell mobilizer
granulocyte colony-stimulating factor (
G-CSF). We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs) in
G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end,
G-CSF alone (50 μg/kg) or in combination with a single dose (10(6) cells) of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min) of the middle cerebral artery.
Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-
stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-
stroke survival period of 56 days. Daily treatment for post-
stroke aged rats with
G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination
therapy also led to robust angiogenesis in the formerly
infarct core and beyond in the "islet of regeneration." However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or
infarct volume and therefore did not further improve the post-
stroke recovery. We suggest that in a real clinical practice involving older post-
stroke patients, successful regenerative
therapies would have to be carried out for a much longer time.