15-07-08(4:43:38)
Authors:
Boltze J 1,2, Wagner DC 1, Foerschler A 3,6, Barthel H 2,4, Nitzsche B 1, Boltze C 1, Reischauer A 5, Hoffmann A 7, Sabri O 4, Emmrich F 1,2, Gille U 7,8
Institutions:
1 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
2 Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany
3 Department of Neuroradiology, University Hospital rechts der Isar, Munich, Germany
4 Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany
5 Institute for Veterinary Pathology, University of Leipzig, Leipzig, Germany
6 Center for Diagnostic Radiology, University of Leipzig, Leipzig, Germany
7 Institute for Veterinary Anatomy, University of Leipzig, Leipzig, Germany
8 VITA 34 Intl. Inc., Leipzig, Germany
Title of abstract : Autologous bone marrow cells delivery reduces sensorimotor deficits and lesion size in a large animal model of stroke
Abstract text:
Introduction
While therapeutic efficacy of xenogeneic bone marrow (BM) cell administration for stroke has recently been shown in rodents, no data for stroke treatment by autologous cell injection in large animal is available. We evaluated benefit of subacute autologous BM cell transplantation in a novel sheep model.
Material & Methods
30 adult rams were subjected to permanent middle cerebral artery occlusion. 15 animals received 4.0×10E6 autologous mononuclear BM cells per kilogram bodyweight after 24 hours. 15 sheep served as controls. Continous behavioral phenotyping as well as repeated MRI and PET imaging (days 1, 14 and 42) were performed for 7 weeks. Thereafter, animals were sacrificed and brains were removed for further histological investigation.
Results
Enhanced functional improvement was observed in cell treated subjects (p<0.01). Despite minor motorfunctional improvement, controls suffered from moderate to severe motor and sensory dysfunctions throughout the observation period. MRI investigations showed similar lesion size in both groups at day 1 (p=0.59), but reduction of lesion size in treatment group 42 days upon MCAO (p<0.01). These findings could furthermore be confirmed by 15O-water- and 18F-Desoxyglucose PET (p<0.05). No adverse event or tumor formation was observed.
Conclusion
Autologous BM marrow administration 24 hours following stroke is safe and effective in sheep. BM cell administration might be used as a novel treatment option in fighting stroke in upcoming clinical trials.
