Yuichi Sasaki1, Masanori Sasaki2, Yuko Kataoka-Sasaki3, Masahito Nakazaki4, Hiroshi Nagahama5, Junpei Suzuki6, Daiki Tateyama7, Shinichi Oka8, Takahiro Namioka9, Ai Namioka10, Rie Onodera11, Takeshi Mikami12, Masahiko Wanibuchi13, Masafumi Kakizawa14, Sumio Ishiai15, Jeffery D Kocsis16, Osamu Honmou17. 1. Y. Sasaki, PT, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan, and Department of Rehabilitation, Sapporo Medical University School of Medicine. 2. M. Sasaki, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, Japan; Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut. msasaki@sapmed.ac.jp. 3. Y. Kataoka-Sasaki, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 4. M. Nakazaki, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 5. H. Nagahama, RT, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 6. J. Suzuki, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 7. D. Tateyama, BS, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 8. S. Oka, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 9. T. Namioka, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 10. A. Namioka, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 11. R. Onodera, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine. 12. T. Mikami, MD, PhD, Department of Neurosurgery, Sapporo Medical University School of Medicine. 13. M. Wanibuchi, MD, PhD, Department of Neurosurgery, Sapporo Medical University School of Medicine. 14. M. Kakizawa, PT, Department of Rehabilitation, Sapporo Medical University School of Medicine. 15. S. Ishiai, MD, PhD, Department of Rehabilitation, Sapporo Medical University School of Medicine. 16. J.D. Kocsis, PhD, Department of Neurology, Yale University School of Medicine, and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System. 17. O. Honmou, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine; Department of Neurology, Yale University School of Medicine; and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System.
Abstract
BACKGROUND: Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat stroke models. Rehabilitation therapy through physical exercise also provides therapeutic efficacy for cerebral ischemia. OBJECTIVE: The purpose of this study was to investigate whether synergic effects of daily rehabilitation and intravenous infusion of MSCs has therapeutic effects after stroke in rats. DESIGN: This was an experimental study. METHODS: A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. Four experimental groups were studied: group 1 (vehicle only, n=10), group 2 (vehicle + exercise, n=10), group 3 (MSCs only, n=10), and group 4 (MSCs + exercise, n=10). Rat MSCs were intravenously infused at 6 hours after MCAO, and the rats received daily rehabilitation with treadmill running exercise for 20 minutes. Lesion size was assessed at 1, 14, and 35 days using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. RESULTS: Both combined therapy and MSC infusion reduced lesion volume, induced synaptogenesis, and elicited functional improvement compared with the groups without MSC infusion, but the effect was greater in the combined therapy group. LIMITATIONS: A limitation of this study is that the results were limited to an animal model and cannot be generalized to humans. CONCLUSIONS: The data indicate that the combined therapy of daily rehabilitation and intravenous infusion of MSCs improved functional outcome in a rat MCAO model.
BACKGROUND: Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in ratstroke models. Rehabilitation therapy through physical exercise also provides therapeutic efficacy for cerebral ischemia. OBJECTIVE: The purpose of this study was to investigate whether synergic effects of daily rehabilitation and intravenous infusion of MSCs has therapeutic effects after stroke in rats. DESIGN: This was an experimental study. METHODS: A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. Four experimental groups were studied: group 1 (vehicle only, n=10), group 2 (vehicle + exercise, n=10), group 3 (MSCs only, n=10), and group 4 (MSCs + exercise, n=10). Rat MSCs were intravenously infused at 6 hours after MCAO, and the rats received daily rehabilitation with treadmill running exercise for 20 minutes. Lesion size was assessed at 1, 14, and 35 days using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. RESULTS: Both combined therapy and MSC infusion reduced lesion volume, induced synaptogenesis, and elicited functional improvement compared with the groups without MSC infusion, but the effect was greater in the combined therapy group. LIMITATIONS: A limitation of this study is that the results were limited to an animal model and cannot be generalized to humans. CONCLUSIONS: The data indicate that the combined therapy of daily rehabilitation and intravenous infusion of MSCs improved functional outcome in a ratMCAO model.