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.
Footnotes
Dr M. Sasaki, Dr Kocsis, and Dr Honmou provided concept/idea/research design and writing. Dr Sasaki, Dr Kataoka-Sasaki, Dr Nakazaki, Dr T. Namioka, and Dr A. Namioka provided data collection. All authors provided data analysis. Dr M. Sasaki provided project management. Dr M. Sasaki, Dr Onodera, and Dr Honmou provided fund procurement. Dr M. Sasaki and Dr Honmou provided facilities/equipment. Dr Ishiai and Dr Honmou provided institutional liaisons. Dr Kocsis provided consultation (including review of manuscript before submission).
This work was supported, in part, by JSPS KAKENHI grant numbers 26350618, 25462226, 24592138, 26462214, and 15K10365; the AMED Translational Research Network Program (B51) and the RR&D Service of Department of Veterans Affairs; the VA SCI Translational Collaborative Consortium for Regenerative Medicine; and the NMSS (grant RG2135 to Dr Kocsis). The authors are thankful to the National BioResource Project–Rat (http://www.anim.med.kyoto-u.ac.jp/NBR/) for providing rat strains (W-Tg[CAG-GFP]184Ys).
- Received September 10, 2015.
- Accepted May 3, 2016.
- © 2016 American Physical Therapy Association
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