Treadmill exercise enhances therapeutic potency of transplanted bone mesenchymal stem cells in cerebral ischemic rats via anti-apoptotic effects.
BACKGROUND
The transplantation of bone marrow stromal cells (MSCs) has proved to ameliorate ischemic brain injury in animals, but most transplanted MSCs undergo apoptosis in the ischemic penumbra, greatly compromising the therapeutic value of this treatment. Meanwhile, cell apoptosis can be inhibited by post-ischemia exercise which has been demonstrated to improve the expression of related anti-apoptotic proteins. The present study investigated whether treadmill exercise enhances the neuroprotective effects of transplanted MSCs in a rat experimental stroke model.


RESULTS
Rats were subjected to 2-h middle cerebral artery occlusion (MCAO). Twenty-four hours after reperfusion, they were assigned randomly to receive no MSCs treatment and no exercise (control group), intravenous transplantation of MSCs and treadmill exercise (MSCs + Ex group), MSCs transplantation only (MSCs group) and treadmill exercise only (Ex group). Neurological assessment, TUNEL staining and western blot were performed. Compared with the MSCs group and Ex group, the MSCs + Ex group reported markedly improved neurological function, significantly decreased apoptotic cells, and increased expressions of survivin and bcl-2 (p < 0.05 or p < 0.01, respectively). Interestingly, the treadmill exercise significantly inhibited the apoptosis of transplanted MSCs. As a result, the number of engrafted MSCs in the MSCs + Ex group was significantly higher than that in the MSC group (p < 0.01).


CONCLUSIONS
Treadmill exercise enhances the therapeutic potency of MSCs by improving neurological function and possibly inhibiting the apoptosis of neuron cells and transplanted MSCs. These effects may involve an increased expression of survivin and bcl-2.
Department of Rehabilitation, Union Hospital, Fujian Medical University, Fuzhou, 350001, People's Republic of China. yixianz1981@sina.com.
Yi-Xian
YX
Zhang
College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People's Republic of China. 16774921@qq.com.
Ming-Zhou
MZ
Yuan
Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou, 350001, People's Republic of China. 45464562@sina.com.
Lin
L
Cheng
Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou, 350001, People's Republic of China. 1145504659@qq.com.
Long-Zai
LZ
Lin
Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou, 350001, People's Republic of China. duwind888@sohu.com.
Hou-Wei
HW
Du
Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou, 350001, People's Republic of China. rongy15@yahoo.com.cn.
Rong-Hua
RH
Chen
Department of Rehabilitation, Union Hospital, Fujian Medical University, Fuzhou, 350001, People's Republic of China. xieheliunan1984@sina.com.|Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou, 350001, People's Republic of China. xieheliunan1984@sina.com.
Nan
N
Liu
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery; D008124:Locomotion / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000077022:Survivin
C516989:Birc5 protein, rat; D008869:Microtubule-Associated Proteins; D000077022:Survivin