Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants |
|Research Institution||OKAYAMA UNIVERSITY |
TOKUNAGA Kouji OKAYAMA UNIVERSITY, OKAYAMA UNIVERSITY HOSPITALS, LECTURER, 医学部・歯学部附属病院, 講師 (40294467)
DATE Isao OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院医歯薬学総合研究科, 教授 (70236785)
SUGIU Kenji OKAYAMA UNIVERSITY, HOSPITALS, LECTURER, 医学部・歯学部附属病院, 講師 (40325105)
MIYOSHI Yasuyuki OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, LECTURER, 大学院医歯薬学総合研究科, 講師 (00362997)
ONODA Keisuke OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, ASSISTANT, 大学院医歯薬学総合研究科, 助手 (20379837)
MATSUI Toshihiro OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, ASSISTANT, 大学院医歯薬学総合研究科, 助手 (80362995)
新郷 哲郎 岡山大学, 医学部・歯学部附属病院, 助手 (50379749)
西尾 晋作 岡山大学, 大学院・医歯学総合研究科, 助手 (80325109)
|Project Period (FY)
2003 – 2006
Completed (Fiscal Year 2006)
|Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
|Keywords||adult / cytokines / neurotrophic facto / GDNF / neuroprotection / MRI / microenvironment / differentiation / 神経幹細胞 / 脳虚血 / 慢性 / シナプス / グリオーシス / ニューロン新生 / 遊走 / アデノウイルス / カスパーゼ / アポトーシス / GFRα / アストロサイト / N-CAM / 細胞移植 / ニューロンへの分化 / 成体 / 神経移植|
For ischemic brain to realize intracerebral cell replacement therapy using neural stem cells, we hypothesized that autologous transplantation using neural stem cells (NSCs) is one of the safest and most useful therapies.
First, neural stem cells were harvested from the subventricular zone of adult rodents or primates, were expanded to the transplantable number of cells in the presence of proliferating factors, and could be differentiated into a large number of neurons using the combination with several kinds of neurotrophic factors and cytokines.
Second, transplantation of adult NSCs had the neuroprotective effects on acute ischemic rat model as the image analyzed (using a clinical 1.5 T MRI), behavioral and histological improvements. The mechanism is that adult NSCs could secrete the various kinds of neurotrophic factors and cytokines (GDNF, EPO, CNTF etc), which had the effects surrounding to the transplanted striatum and cortex.
Third, We established the GDNF, which has a one of the mo
st neurotrophic effect for the ischemic neurons, producing NSCs (NSC-GDNF) using GDNF gene transfection method. The transplantation of NSC-GDNF had a neuroprotective effect in the acute ischemic model as the image analyzed, behavioral, and histological improvements. GDNF secreted from NSC-GDNF also had a strong differentiation effect into mature neurons and a migrating effect to a distance. The mechanism is that NSC-GDNF transplantation may change the microenvironment into the ischemic brain.
Finally, intracerebral transplantation of adult NSCs has a restorative effect for the chronic ischemic brain as the behavioral and histological improvements. The mechanism is that the transplanted NSC may not only differentiated into the mature neurons and have the synapse formation between the differentiated neurons and host neurons, but also change the microenvironments and enhance the host plasticity
These results suggested that autologous-transplantation of adult neural stem cells is useful in the treatment of ischemic brain. Less