Open Access Research

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

Daniel-Christoph Wagner12*, Mitja Bojko1, Myriam Peters1, Marlene Lorenz1, Cornelia Voigt13, Alexander Kaminski4, Dirk Hasenclever5, Markus Scholz5, Alexander Kranz12, Gesa Weise12 and Johannes Boltze12

Author Affiliations

1 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

2 Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany

3 Department of Urology, University of Leipzig, Leipzig, Germany

4 Department of Cardiac Surgery, University of Rostock, Rostock, Germany

5 Institute for Medical Informatics, Statistics & Epidemiology, University of Leipzig, Leipzig, Germany

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Experimental & Translational Stroke Medicine 2012, 4:17  doi:10.1186/2040-7378-4-17

Published: 24 August 2012

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.

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