2022 Fiscal Year Research-status Report
Rewiring the brain: remote-controlled axon guidance by magnetic nanoparticles to improve Parkinson's therapies
| Project/Area Number |
22K06430
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Keywords | Dopaminergic neurons / Stem cells (iPSCs) / Magnetic nanoparticles / Halbach magnet / Axon guidance / CNS regeneration / Parkinson's disease / Nanotechnology |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
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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| Strategy for Future Research Activity |
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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| Causes of Carryover |
The in vitro analysis is established and currently performed. We are planning to increase the number of parallel experiments and therefore, more magnetic devices and nanoparticles are required.
Further, we are planning experiments in Parkinson model rats that need to be purchased.
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[Presentation] Spatiotemporal control of RAS pathway activation by biofunctionalized nanoparticles for guided neurite growth, maturation, and regeneration2022
Author(s)
Fabian Raudzus (presenter), Hendrik Schoeneborn, Sebastian Neumann, Hiromasa Adachi, Emilie Secret, Oliver Brylski, Christine Menager, Jean-Michel Siaugue, Rolf Heumann, Jun Takahashi
Organizer
Horizons in Neuroscience: Organoids, Optogenetics and Remote Control - German Society for Biochemistry and Molecular Biology (GBM e.V.)
Int'l Joint Research / Invited
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