title: Bone marrow-derived mononuclear cells do not exert acute neuroprotection after stroke in spontaneously hypertensive rats.
abstract: Bone marrow-derived mononuclear cells (BM-MNCs) were shown to improve the outcome in animal stroke models and clinical pilot studies on BM-MNCs for stroke patients were already conducted. However, relevant aspects of pre-clinical evaluation, such as the use of animals with comorbidities and dose-response studies, were not thoroughly addressed so far. We therefore investigated different BM-MNC doses in the clinical meaningful stroke model of spontaneously hypertensive (SH) rats. Three hours after the onset of transient middle cerebral artery occlusion (MCAO) animals received either one of three syngeneic BM-MNC doses or placebo intravenously. The primary endpoint was the infarct size. Secondary endpoints included functional outcome, mortality, inflammatory processes, and the dose-response relationship. In contrast to previous studies which used healthy animals no beneficial effect of BM-MNCs was found. Infarct volumes, mortality, behavioral outcomes, and the extent of the inflammatory response to cerebral ischemia were comparable in all groups. In conclusion, we could not demonstrate that early BM-MNC treatment improves the outcome after stroke in SH rats. Whether BM-MNCs improve neurological recovery after delayed treatment initiation was not investigated in the present study, but our data indicates that this should be determined in co-morbid animal stroke models before moving to large-scale clinical studies. Future preclinical stroke studies on co-morbid animals should also include groups of healthy animals in order to determine whether negative results can be attributed to the comorbid condition.
authors.affiliation: Klinik für Neurologie, Department of Neurology, University of Münster Münster, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Minnerup
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology and Translational Centre for Regenerative Medicine, University of Leipzig Leipzig, Germany.
authors.forename: Daniel-Christoph
authors.initials: DC
authors.lastname: Wagner
authors.affiliation: Klinik für Neurologie, Department of Neurology, University of Münster Münster, Germany.
authors.forename: Jan-Kolja
authors.initials: JK
authors.lastname: Strecker
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology and Translational Centre for Regenerative Medicine, University of Leipzig Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pösel
authors.affiliation: Klinik für Neurologie, Department of Neurology, University of Münster Münster, Germany ; CATO Europe GmbH Cologne, Germany.
authors.forename: Sevgi
authors.initials: S
authors.lastname: Sevimli-Abdis
authors.affiliation: Klinik für Neurologie, Department of Neurology, University of Münster Münster, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Klinik für Neurologie, Department of Neurology, University of Münster Münster, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schilling
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology and Translational Centre for Regenerative Medicine, University of Leipzig Leipzig, Germany ; Massachusetts General Hospital and Harvard Medical School Charlestown, MA, USA.
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.affiliation: Klinik für Neurologie, Department of Neurology, University of Münster Münster, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Diederich
authors.affiliation: EVK Bielefeld, Bethel, Neurologische Klinik Bielefeld, Germany.
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
keywords: bone marrow-derived mononuclear cells; dose-response; middle cerebral artery occlusion; spontaneously hypertensive rats; stroke