研究課題/領域番号 |
22K06430
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研究種目 |
基盤研究(C)
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配分区分 | 基金 |
応募区分 | 一般 |
審査区分 |
小区分46010:神経科学一般関連
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研究機関 | 京都大学 |
研究代表者 |
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研究分担者 |
土井 大輔 京都大学, iPS細胞研究所, 特定拠点講師 (10587851)
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研究期間 (年度) |
2022-04-01 – 2025-03-31
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研究課題ステータス |
交付 (2022年度)
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配分額 *注記 |
4,030千円 (直接経費: 3,100千円、間接経費: 930千円)
2024年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2022年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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キーワード | Dopaminergic neurons / Stem cells (iPSCs) / Magnetic nanoparticles / Halbach magnet / Axon guidance / CNS regeneration / Parkinson's disease / Nanotechnology / Cell Replacement Therapy / Parkinson's Disease / Magnetic Nanoparticles / Pluripotent Stem Cells / Neuronal Regeneration |
研究開始時の研究の概要 |
To rewire the brain, we aim for the remote-controlled guidance of neurite growth by magnetic nanoparticles (MNPs). When an external magnetic field is applied, these MNPs generate forces at the cell membrane which promote neurite growth and increase neurite extension in the direction of the magnetic field. The aim is to adept this system for single induced dopaminergic neurons and neurospheres. We will use the obtained knowledge and transplant the MNP-loaded neurospheres in Parkinson’s disease model rats to rewire the disconnected brain regions.
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研究実績の概要 |
Within the first year of the grant, various important steps were performed that serve as the prerequisite and basis for the project. 1) Suitable magnetic nanoparticles were acquired. Two types of nanoparticles turned out to be tolerated by the cells without any notable side effects. 2) The magnetic applicator was designed and built. The first 3D-printed version was unfortunately not successful. Therefore, two devices from aluminum were constructed. Now, these devices have an improved and more homogenous magnetic field. 3) The application of nanoparticles to dopaminergic progenitors was established and optimized. The most difficult part of the attachment of spheres is finally solved. 4) First magnetic manipulations are performed, and the optimization of different parameters is ongoing.
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現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
Two issues resulted in a slight delay: 1) The first Halbach magnet array turned out to be not sufficient for the project. Although the construction and used materials were reported by others, the 3D-printed housing of the magnets started to show signs of deformation after some time in use. In addition, the magnets were not available and had to be custom-made. However, the issues have been solved, and the new magnetic device is superior with respect to the homogeneity of the magnetic field. 2) The loading of dopaminergic neurospheres had to be optimized. In addition, the reattachment of floating spheres to a coated surface was extremely inefficient. A robust attachment protocol needed to be developed.
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今後の研究の推進方策 |
As all prerequisites are now available, the experiments can now be performed according to the proposed schedule: 1) Refinement of magnetic nanoparticle-induced stretch growth of dopaminergic progenitors 2) Establishing an optimized method to attach a suitable magnet to rats. 3) Transplantation of nanoparticle-loaded neurospheres into rat brains. 4) Behavioral and histological analysis of cell replacement therapy without and with magnetic field.
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