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Impact of age on the efficacy of bone marrow mononuclear cell transplantation in experimental stroke

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Author(s): Wagner Daniel-Christoph | Bojko Mitja | Peters Myriam | Lorenz Marlene | Voigt Cornelia | Kaminski Alexander | Hasenclever Dirk | Scholz Markus | Kranz Alexander | Weise Gesa | Boltze Johannes

Journal: Experimental & Translational Stroke Medicine
ISSN 2040-7378

Volume: 4;
Issue: 1;
Start page: 17;
Date: 2012;
Original page

Keywords: Brain ischemia | Cell transplantation | Bone marrow cell transplantation | Age | Comorbidity | SHR

ABSTRACT
Abstract Bone marrow-derived mononuclear cells (BM MNC) have been effectively used to treat experimental stroke. Most of the preclinical trials have been performed in young and healthy laboratory animals, even though age and hypertension are major risk factors for stroke. To determine the influence of age on the properties of BM MNCs after cerebral ischemia, we compared the efficacy of aged and young BM MNC in an in vitro model of cerebral hypoxia and in an adapted in vivo model of stroke. Human BM MNCs were obtained from healthy young or aged donors and either co-cultured with rat hippocampal slices exposed to oxygen glucose deprivation (OGD), or transplanted intravenously 24 h after permanent middle cerebral artery occlusion in aged (18 months) spontaneously hypertensive rats (SHR). Efficacy was examined by quantification of hippocampal cell death, or respectively, by neurofunctional tests and MR investigations. Co-cultivation with young, but not with aged BM MNCs significantly reduced the hippocampal cell death after OGD. Transplantation of both young and old BM MNCs did not reduce functional deficits or ischemic lesion volume after stroke in aged SHR. These results suggest a significant impact of age on the therapeutic efficacy of BM MNCs after cerebral ischemia.

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