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1

Transplantation of autologous bone marrow stromal cells (BMSC) for ischemic stroke - strategy and tactics for clinical application

100%
Kuroda S.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 1
Objective: There is increasing evidence that the transplanted bone marrow stromal cells (BMSC) significantly promote functional recovery after central nervous system damage in the animal models of various kinds of CNS disorders, including cerebral infarct. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with neurological disorders. In this meeting, therefore, we discuss what we should clarify to establish cell transplantation therapy in clinical situation and describe our recent works for this purpose. Methods and Results: The BMSC have multiple abilities to differentiate into the neural cells and to promote neuronal survival and axon elongation, contributing to rebuild the neural circuits in the injured CNS. Using optical imaging and MRI techniques, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. Clinical MR apparatus can visualize the tagged BMSC in the brain. FDG PET is quite valuable to monitor the recovery of brain metabolism after transplantation. The BMSC can be expanded using the animal protein-free culture medium within a clinically relevant period. G-CSF is useful to enhance their proliferation when the BMSC are obtained from the aged patients. There are optimal dose and timing of BMSC transplantation to yield significant therapeutic benefits. Conclusion: It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation to establish it as a definite therapeutic strategy in clinical situation in very near future.
2

Bone marrow stromal cell transplantation for ischemic stroke - its multi-functional feature

100%
Kuroda S.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 1
In this article, the author reviews recent advancements of basic research on bone marrow stromal cell (BMSC) transplantation for ischemic stroke. The BMSCs are easily isolated from the patients themselves and transplanted into them without any ethical and immunological problem. Animal experiments have shown that BMSC transplantation significantly enhance the recovery of motor and/or cognitive function in various types of neurological disorders such as ischemic stroke. The transplanted BMSCs aggressively migrate toward the damaged tissue and proliferate in the host brain. The BMSCs significantly improve the neuronal receptor function and local glucose metabolism in the peri-infarct area when transplanted into the infarct brain. Recent studies strongly suggest that the BMSCs contain heterogeneous subpopulations and contribute to functional recovery through multiple mechanisms, including neuroprotection, inflammatory modulation, cell fusion, and neural differentiation. The author describes the importance to establish BMSC transplantation as a therapeutic entity that is scientifically proven.
3

Bone marrow stromal cell transplantation enhances recovery of motor function after lacunar stroke in rats

45%
Shichinohe H., Yamauchi T., Saito H., Houkin K., Kuroda S.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 3
This study was aimed to clarify if the bone marrow stromal cells (BMSCs) significantly improve functional outcome after lacunar stroke when stereotactically transplanted into the brain. Ouabain, a Na/K ATPase pump inhibitor, was stereotactically injected into the right striatum of Wistar rats. One week later, the superparamagnetic iron oxide (SPIO)-labeled rat BMSCs («=7) or vehicle (n=8) were stereotactically transplanted into the left striatum. Using rotarod test, motor function was serially evaluated through the experiment. A 7.0-T MR apparatus was employed to serially monitor the migration of BMSCs in the host brain. Histological analysis was performed at 7 weeks after ouabain injection, i.e., 6 weeks after BMSC transplantation. Ouabain injection yielded the reproducible, focal lesion in the right striatum, causing continuous motor dysfunction throughout the experiment. BMSC transplantation significantly enhanced the recovery of motor function after ouabain injection. MR imaging demonstrated that the BMSCs aggressively migrated towards the lesion through the corpus callosum. Histological analysis supported the findings on MRI. The BMSCs significantly enhanced the neurogenesis in the subventricular zone (SVZ) on both sides. Some of them also expressed neuronal or astrocytic phenotypes in the neocortex, SVZ, corpus callosum, and peri-lesion area. These findings strongly suggest that the BMSCs may serve therapeutic impacts on lacunar stroke when stereotactically transplanted at clinically relevant timing.
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