Abstract
BackgroundIncreasing 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.MethodsAdult 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.ResultsBody 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.ConclusionsThis 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.
Highlights
Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction
To meet the translational roadblocks we aimed to investigate the efficacy of a cell therapy in a rat stroke model that was shown to be logistically feasible and efficient in a clinical study of patients with myocardial infarction
There was no significant difference in the temperature during surgery between cell-treated animals and controls
Summary
Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction. Stroke is the second leading cause of death after myocardial infarction and the most frequent cause of adult disability [1,2] For both cardiovascular and cerebrovascular disease cell therapy emerged as a promising therapeutic option [3,4,5]. To meet the translational roadblocks we aimed to investigate the efficacy of a cell therapy in a rat stroke model that was shown to be logistically feasible and efficient in a clinical study of patients with myocardial infarction. As performed in the REPAIR-AMI trial we used an intraarterial injection for cell transplantation This approach is routinely performed by neurointerventionalists for drug delivery and was shown to be feasibly and safe in acute stroke patients
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