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Rewiring the brain: remote-controlled axon guidance by magnetic nanoparticles to improve Parkinson's therapies

Research Project

Project/Area Number 22K06430
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionKyoto University

Principal Investigator

Raudzus Fabian  京都大学, 医学研究科, 助教 (10906358)

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)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsParkinson's Disease / Magnetic Nanoparticle / Cell Replacment / Stem Cells / Dopaminergic Neurons / Dopaminergic neurons / Stem cells (iPSCs) / Magnetic nanoparticles / Halbach magnet / Axon guidance / CNS regeneration / Parkinson's disease / Nanotechnology / Cell Replacement Therapy / Magnetic Nanoparticles / Pluripotent Stem Cells / Neuronal Regeneration
Outline of Research at the Start

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.

Outline of Annual Research Achievements

In the FY2023, large efforts were made towards the magnetic manipulation of nanoparticle-loaded dopaminergic neurospheres. In close collaboration with the Raffa Lab (Pisa, Italy) we were able to show the asymmetric neurite growth in direction of the magnetic field.
As the transition to animal models requires further optimization, we performed the magnetic manipulation in ex vivo cultures. These cultures are 350 um thick sections of the mouse brain. Nanoparticle=loaded spheres were grafted into these ex vivo cultures. We were able to see neurite growth in the direction of the magnetic field.
In summary, in the FY2023, we were able to translate our approach to the neurosphere model and were able to show that the stretch growth is still presence in an organotypic environment.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

As mentioned above, we were able to tackle the two major points proposed for FY2023. On the one hand, the magnetic manipulation of neurospheres was done. On the other hand, the first step towards the application of our approach in vivo was tested. Now, the actual application in vivo can be tested.

Strategy for Future Research Activity

The first step is generating more data with our neurosphere and ex vivo ex vivo model. After optimizing the parameters, we can translate the approach to the animal model. Here, the biggest task is to finalize designing an appropriate magnetic applicator.

Report

(2 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (10 results)

All 2024 2022 Other

All Int'l Joint Research (5 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Int'l Joint Research] University of Pisa/Vittoria Raffa Lab(イタリア)

    • Related Report
      2023 Research-status Report
  • [Int'l Joint Research] Johannes Gutenberg University Mainz/Peter Bluemler(ドイツ)

    • Related Report
      2023 Research-status Report
  • [Int'l Joint Research] Ruhr University Bochum/Rolf Heumann(ドイツ)

    • Related Report
      2023 Research-status Report
  • [Int'l Joint Research] Johannes Gutenberg University Mainz(ドイツ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Universita' Degli Studi Di Pisa(イタリア)

    • Related Report
      2022 Research-status Report
  • [Journal Article] A comprehensive approach to characterize navigation instruments for magnetic guidance in biological systems2024

    • Author(s)
      Bluemler Peter、Raudzus Fabian、Schmid Friederike
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 7879-7879

    • DOI

      10.1038/s41598-024-58091-x

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Optimization of Cell Replacement Therapies in the CNS: Magnetic Nanoparticles and Signaling Pathway Modulation2024

    • Author(s)
      Fabian Raudzus
    • Organizer
      Seminar of the Biology Institute, University of Pisa, Italy
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] Optimization of Cell Replacement Therapies in the CNS: Magnetic Nanoparticles and Signaling Pathway Modulation2024

    • Author(s)
      Fabian Raudzus
    • Organizer
      Seminar at the Max Planck Institute of Biochemistry, Martinsried, Germany
    • Related Report
      2023 Research-status Report
    • Invited
  • [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.)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Neue Ansaetze aus Bochum zur Optimierung von Zellersatztherapien bei Morbus Parkinson in Kyoto2022

    • Author(s)
      Fabian Raudzus
    • Organizer
      30th Anniversary of Biochemistry - Ruhr-University Bochum
    • Related Report
      2022 Research-status Report
    • Invited

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Published: 2022-04-19   Modified: 2024-12-25  

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