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Granulocyte colony-stimulating factor and bone marrow mononuclear cells for stroke treatment in the aged brain

: Buga, Ana Maria; Scheibe, Johanna; Möller, Karoline; Ciobanu, Ovidiu; Pösel, Claudia; Boltze, Johannes; Popa-Wagner, Aurel


Current neurovascular research 12 (2015), No.2, pp.155-162 : Ill.
ISSN: 1567-2026 (print)
ISSN: 1875-5739 (online)
Journal Article
Fraunhofer IZI ()
stem cells; bone marrow; stroke; regenerative therapy; translational medicine

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.