| Project/Area Number |
16K08267
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Pharmacology in pharmacy
|
|---|
| Research Institution | Kobe Pharmaceutical University (2017-2018)
Kyoto University (2016) |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
Kinoshita Shinichi
Fukuzawa Moeka
Inose Yuri
Yamamoto Ayaka
Ichimura Suzuka
Nishisako Kazuma
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | ノックイン / ゲノム編集 / 細胞移植 / パーキンソン病 / ドパミンニューロン / 神経突起伸長 / 薬理学 |
|---|
| Outline of Final Research Achievements |
We have previously clarified that the cell adhesion factor, integrin α5β1, is involved in dopaminergic innervation of striatal neurons. Therefore, transplantation of integrin α5-overexpressing dopamine neurons into the striatum of patients with Parkinson's disease is expected to improves the therapeutic effect. In this study, we prepared mouse embryonic stem (ES) cells in which the integrin α5 gene was knocked in to the dopamine transporter gene. When the knock-in cells were differentiated into dopamine neurons, the expression of the integrin α5 gene was observed. In addition, the ES cell-derived cells were transplanted into Parkinson's disease model mice. When mitomycin C-treated cells were transplanted as cell aggregation, tumorigenesis was suppressed and engraftment was achieved.
|
| Academic Significance and Societal Importance of the Research Achievements |
現在の幹細胞由来の細胞移植治療では、安全第一のため外来性遺伝子を排除する方向で進んでいる。しかし、本研究では、移植する細胞の機能を亢進させるための遺伝子導入法を検討した。成果として、細胞移植実験に適したノックインES細胞の作製および分化・移植方法の確立ができたと考える。今後、通常の細胞よりも高機能化した遺伝子導入細胞を移植することの有用性を示せれば、パーキンソン病への細胞移植にとどまらず、将来の細胞移植治療の選択肢を広げることになると予想される。
|
