Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||OKAYAMA UNIVERSITY|
SUGIU Kenji OKAYAMA UNIVERSITY, HOSPITALS, LECTURER, 医学部・歯学部附属病院, 講師 (40325105)
DATE Isao OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, PROFESSOR, 医学部・歯学部附属病院, 教授 (70236785)
TOKUNAGA Kouji OKAYAMA UNIVERSITY, HOSPITALS, LECTURER, 医学部・歯学部附属病院, 講師 (40294467)
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 / tyrosine hydroxylase / dopamine / GDNF / neurotrophic factor / microenvironment / CREB / differentiation / 神経幹細胞 / パーキンソン病 / 神経修復 / 脳室下帯 / 成体 / 自家移植 / アデノウイルス / アストロサイト / 神経保護 / 相乗効果 / 細胞移植 / ニューロンへの分化 / 神経移植|
For Parkinson's disease (PD) 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.
We showed the following:
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 dopaminergic neurons using tyrosine hydroxylase-inducing factor.
Second, transplantation of adult NSCs had the neuroprotective effects as the 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.
Third, We established the GDNF, which has a one of the most neurotrophic effect on the dopaminergic neurons, producing NSCs (NSC-G
DNF) using GDNF gene transfection method. The transplantation of NSC-GDNF had a neuroprotective effect in the parkinsonian model animals as the behavioral and histological improvements. GDNF secreted from NSC-GDNF also had a strong surviving and migrating effect for the grafted cells and migrating. The mechanism is that NSC-GDNF transplantation may change the microenvironment into the lesioned striatum and the accommodated host glial cells may release the other trophic factors except for GDNF.
Finally, transplantation of dopaminergic (DA) neurons derived from adult NSCs has a restorative effect for the parkinsonian rat model. The survival of the grafted DA neurons derived from NSCs was poor in the lesioned striatum, but the great number of synapse formation between the grafted DA neurons and host neurons were observed. The mechanism is that upregulation of BDNF and phosphorylated CREB may enhance the synaptogenesis.
These results suggested that autologous transplantation of adult neural stem cells is useful in the treatment of PD. Less