Magnetogenetics: how neural stem cells grow in a certain direction

Interview with Prof. Jacob Piehler, University of Osnabrück

If you could stimulate brain cells to grow in a specific direction, you would probably be able to achieve a significant improvement in the health of patients suffering from Parkinson’s disease. This is why the MAGNEURON project focuses on this approach. The EU is funding the project with approximately 3.5 million Euros. Biophysicist Professor Jacob Piehler of the University of Osnabrück has also done research in this field. has asked him about the current project status.


Photo: Prof. Jacob Piehler

Jacob Piehler; © Siegfried Engelbrecht-Vandré/Universität Osnabrück

Professor Piehler, could you briefly describe the goal of the MAGNEURON project.

Jacob Piehler: The goal of the project is to develop a new technology with which neural stem cells can be grown and differentiated a certain way. To do this, we are developing magnetic nanoparticles, which we functionalize so they activate very specific signaling pathways in the cells that are responsible for these differentiation and growth processes.

Four institutes are participating in this project. What is your assignment?

Piehler: Here in biophysics, our job is to develop the fundamental methodology and use these nanoparticles to explicitly build functional signal transduction platforms that are able to transmit specific signals in the cell.

How are the nanoparticles functionalized?

Piehler: We either immobilize capture molecules on these nanoparticles that subsequently capture the respective effector proteins from the target cell or we immobilize recombinant effector proteins directly on these nanoparticles. These are primarily proteins that control signaling pathways of neurotrophic factors, e.g., the small G protein H-ras or its effector proteins.

How much progress have you made already?

Piehler: We are still in the early stages of this project. In a publication two years ago, we were able to show that we are able to induce G-protein-based signal transduction by means of magnetic manipulation of the cell. In reference to optogenetics, we call this method magnetogenetics.

How will patients, who suffer from Parkinson’s disease, for example, benefit from this development?

Piehler: We know that stem-cell therapy would essentially be possible for Parkinson’s disease if we could get the respective stem cells to grow axons in the right direction. Experiments with primates were successful. However, those were random positive results because we are not yet able to affect the direction of differentiated nerve cells. Our starting point with magnetogenetic manipulation is to find the "right direction".

What would a therapy look like?

Piehler: First, we would load the patient’s reprogrammed stem cells with functionalized nanoparticles. They would subsequently be inserted into the striatum. This is already medically feasible. The actual medical technology challenge is to generate a magnetic field that allows you to remotely control the particles in the striatum.

What are the next steps you need to take?

Piehler: First, we want to demonstrate the basic feasibility of this method in neuronal cell cultures. Next, we want to test how we can insert the nanoparticles most efficiently into the stem cells. In addition, we have to monitor that the nanoparticles remain functional in the stem cells over several days. And there is one very important question: are we really able to control nanoparticles in the brain using magnetic fields? Are we able to generate field gradients that are strong enough to reach all the way into the striatum? There are still several technical challenges we need to master.
Photo: Simone Ernst; Copyright: B. Frommann

© B. Frommann

The interview was conducted by Simone Ernst and translated by Elena O'Meara.