Regenerative medicine for cerebral infarction: Stem cell transplantation in the rat model of middle cerebral artery occlusion

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Cerebral stroke frequently occurs in Japanese elderly people and lowers quality of life of the patients. Functional recovery is rarely seen, so the increasing number of the patients is one of the major problems in the modern society. Regenerative medicine may induce the regeneration of disturbed neurons and give us hope for functional recovery even after cerebral stroke. We made a stroke model of middle cerebral artery occlusion in rats with nylon suture method. At Day 1-2, human-derived neuronal cell line, such as neural stem cell line (F3), mesenchymal stem cell line (HB10) and microglial cell line (HMO) was intravenously injected. The transplantation significantly improve the symptom evaluated with the Neurological Severity Score after Day 7. Transplanted cells migrated into the stroked brain; at Day 3, every type of injected cells was seen in stroke border zone area, but at Day 7, HB10 cells and HMO cells already disappeared there. Only F3 cells survived until Day 14. TUNEL stainin … More g indicated that transplantation decreased the apoptotic cells found in the area, which may mean neuroprotection by transplanted cells. Molecular biological analysis was performed to evaluate expressional level of neurotrophic factors. Rat-derived neurotrophic factors such as epidermal growth factor, insulin-like growth factor-1 and granulocyte-colony stimulating factor significantly increased in the penumbra area compared to human-derived growth factors. Inflammatory factors were also investigated with immnohistochemistry after F3 transplantation. Cyclooxygenase-2 (Cox-2) expression was decreased in the infiltrated macrophages and activated microglia in the penumbra area. Iducible nitric oxide synthase (iNOS) expression was also decreased in the endothelial cells. F3 transplantation decreased the number of infiltrated neutrophils around the stroke area, leading to inhibit the inflammatory reaction. In the present study, we demonstrated the several mechanisms why cell transplantation induced recovery from cerebral infarction using rat stroke model. We also presented in the conferences and published the articles about the stroke during the two years. We are further undergoing our study to understand the mechanism of cerebral infarction and neuroprotection by the cell regenerative therapy Less