Title:Granulocyte Colony-stimulating Factor and Bone Marrow Mononuclear Cells for Stroke Treatment in the Aged Brain
Volume: 12
Issue: 2
Author(s): Ana-Maria Buga, Johanna Scheibe, Karoline Moller, Ovidiu Ciobanu, Claudia Posel, Johannes Boltze and Aurel Popa-Wagner
Affiliation:
Keywords:
Stem cells, bone marrow, stroke, regenerative therapy, translational medicine.
Abstract: Ischemic stroke swiftly induces a wide spectrum of pathophysiological sequelae, particularly in the aged brain.
The translational failure of experimental therapies, might partially be related to monotherapeutic approaches, not address
potential counter-mechanisms sufficiently or within the best time window. For example, therapeutic effects relying on
stem/progenitor cell mobilization by granulocyte-colony stimulating factor (G-CSF), require approximately a week to become
manifest, which is potentially beyond the optimal timing. Here, We tested the hypothesis that treating post-stroke
aged rats with the combination of bone marrow-derived mononuclear cells (BM MNC) and G-CSF improves the long
term (56 days) functional outcome by compensating the delay before G-CSF effects come to full effect. 1x106 syngeneic
BM MNC per kg bodyweight (BW) with G-CSF (50µg/kg, given intraperitoneal by via the jugular vein to aged Sprague-
Dawley rats, six hours post-stroke. This process was repeated daily, for a 28 day period. Infarct volume was measured by
magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunohistochemistry at day 56. Functional
recovery was tested during the entire post-stroke survival period. Daily G-CSF treatment led to a robust and consistent
improvement of neurological function, but did not alter final infarct volumes. The combination of G-CSF and BM MNC,
did not further improve post-stroke recovery. The lack of an additional benefit may be due to interaction between both approaches,
and to a lesser extent, in the insensitivity of the aged brains’ regenerative mechanisms. Also considering recent
findings on other tandem approaches involving G-CSF in animal models featuring relevant co-morbidities, we conclude
that such combination therapies are not the optimal approach to treat the acutely injured aged brain.
