A collaborative study led by Professor Vittoria Raffa at the University of Pisa and Assistant Professor Fabian Raudzus (Department of Clinical Application) has unveiled a novel approach that uses magnetically guided mechanical forces to direct axonal growth, aiming to enhance the effectiveness of stem cell-based therapies for Parkinson's disease (PD) and other neurological conditions.
Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN), which project to the striatum (ST) via the nigrostriatal pathway. The loss of these connections leads to dopamine deficiency and the onset of motor symptoms.
While cell replacement therapies using human stem cell-derived dopaminergic progenitors have shown encouraging results in clinical trials, a key limitation remains: the inability to guide the axons of transplanted cells over long distances to their appropriate targets in the adult brain.
To address this, the researchers developed a technique—called nano-pulling—to leverage magnetic nanoparticles (MNPs) and external magnetic fields to apply controlled mechanical forces within transplanted neural cells, thereby guiding their axonal extensions to target brain regions.
To test this system, the research team first constructed an organotypic brain slice model that mimics early-stage PD by co-culturing brain sections containing SN and ST. They transplanted human neuroepithelial stem (NES) cells, preloaded with MNPs, into the SN region. Upon exposure to a magnetic field, the MNPs generated piconewton-scale forces within the cells, stimulating axonal growth in the direction of the magnetic gradient.
The study, now published in Advanced Science, found that nano-pulling significantly enhanced the length and alignment of neural projections toward the striatum. Transplanted cells exhibited increased branching, greater synaptic vesicle formation, and improved microtubule stability—key indicators of neuronal maturation and functional integration.
To read more, click here.