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Open Access Research

Intracarotid administration of human bone marrow mononuclear cells in rat photothrombotic ischemia

Jens Minnerup1*, Florian H Seeger2, Katharina Kuhnert1, Kai Diederich1, Matthias Schilling1, Stefanie Dimmeler3 and Wolf-Rüdiger Schäbitz4

Author Affiliations

1 Department of Neurology, University of Münster, Albert-Schweitzer-Straße 33, 48149 Münster, Germany

2 Division of Cardiology, Department of Medicine, Goethe University, Theodor-Stern-Kai 7 D-60590 Frankfurt (Main) Germany, Germany

3 Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Theodor-Stern-Kai 7 D-60590 Frankfurt (Main) Germany, Germany

4 Department of Neurology, University of Münster and Evangelisches Krankenhaus Bielefeld, Burgsteig 13, 33617 Bielefeld, Germany

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Experimental & Translational Stroke Medicine 2010, 2:3 doi:10.1186/2040-7378-2-3

Published: 2 February 2010

Abstract

Background

Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction. So far only small pilot trials tested the effects of cell therapy in stroke patients, whereas large clinical trials were conducted in patients with ischemic heart disease. To investigate the therapeutic benefit of cell therapy to improve the recovery after stroke, we determined the efficacy of bone marrow derived mononuclear cells, which were shown to improve the recovery in experimental and clinical acute myocardial infarction studies, in a rat stroke model.

Methods

Adult male Wistar rats were randomly assigned to receive either five million human bone marrow mononuclear cells (hBMC) or placebo intraarterially 3 days after photothrombotic ischemia. For immunosuppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24 hours before the cell transplantation. A battery of behavioral tests was performed before and up to 4 weeks after ischemia.

Results

Body temperature and body weight revealed no difference between groups. Neurological deficits measured by the Rotarod test, the adhesive-removal test and the cylinder test were not improved by hBMC transplantation compared to placebo.

Conclusions

This study demonstrates that hBMC do not improve functional recovery when transplanted intraaterially 3 days after the onset of focal cerebral ischemia. A possible reason for the failed neurological improvement after cell therapy might be the delayed treatment initiation compared to other experimental stroke studies that showed efficacy of bone marrow mononuclear cells.