two teams of CONICET Researchers belonging to the Institute of Physics of Silver (IFLP, CONICET-UNLP) and to the Institute of Biological Chemistry and Physical Chemistry “Prof. Alejandro C. Paladini ”(IQUIFIB, CONICET-UBA) has just taken an important step in development of a therapy with potential application in regenerative medicine, when successfully tested on a sciatic nerve injury of rats.
Marcela B. Fernández van Raap, is a reference in nanomagnetism at CONICET at the IFLP, and one of the authors of the research. Paula Soto, completed her doctorate at IQUIFIB with a CONICET scholarship and was the first author of the work. And Patricia Setton-Avruj, a researcher at CONICET and director of the Laboratory of Multipotent Cells in Neuroregeneration at IQUIFIB, also authored the work.
The therapeutic strategy consists of implanting adult stem cells, previously obtained from adipose tissue, that is, body fat, loaded with magnetic nanoparticles and then directed externally through a magnet to the site of damage. The study, published recently in Biomaterials Minutes and selected among thousands by the prestigious magazine Science Commenting on it in its last issue, it was possible to verify that the technique contributes to the recovery of the nerve’s morphology and its functionality.
Research to find therapies that allow nerve regeneration, from the use of adult stem cells, run into a major obstacle: they cannot guarantee the permanence of a sufficient number of cells at the injury site for the time necessary to produce the therapeutic effects .
In the recently published work, the experts combined their previous experiences in, on the one hand, the transplantation of adult stem cells for the regeneration of peripheral nerves and, on the other, the use of magnetic materials in biomedical applications “with the sole aim of improving the arrival and retention of stem cells that have regenerative properties of interest for therapy at the injury site”, according to Fernández van Raap.
The first stage of therapy, tested at Vivo in adult laboratory rats, it consisted of obtaining a type of multipotent adult cells that have the ability to differentiate into several cell types that regulate the immune response, mechanisms of action proposed to exert its regenerative effect. The extraction was performed from the adipose tissue of the same injured animals, in a procedure similar to liposuction.
Once obtained, the cultured cells were incubated with magnetic nanoparticles of magnetite, or iron oxide, a biocompatible material with low toxicity.
“When they come into contact, the cells endocytize the nanoparticles, that is, they deform their cell membranes, envelop and incorporate them. They ‘eat’ them. That’s why we say that cells become magnetic, because now they have nanoparticles inside them”, explains Soto.
“This results in a hybrid material that has distinct properties: on the one hand, those of cells with their growth factors and immunomodulating effects and, on the other hand, the magnetism of nanoparticles, which enables external activation with a magnetic field” , adds Fernández van Raap.
As Setton-Avruj explains, “In previous experiments with intravenous multipotent cell transplants, we have shown that they are recruited or summoned to the site of injury by biological signals generated as a consequence of the inflammatory reaction provoked there. The injured nerve secretes those signals that attract the cells. transplanted cells. The fact that we have managed to magnetize the cells allows them to be transported and manipulated from the outside with the magnet, which helps make their arrival more efficient, as they are retained in the area longer and can have a more significant beneficial effect ” , highlights.
Once the cells loaded with the nanoparticles had been characterized and the amounts incorporated by the cells had been established, they were transplanted into the bloodstream by intravenous injection, and the magnet was placed on the outside of the animal’s paw, in the area of the lesion, with a dressing for 24 hours to attract and hold them in place. “It is a non-invasive procedure, does not require surgery or immobilization and does not cause pain or suffering”, emphasize the specialists.
One of the encouraging results of this innovative strategy was that after a week and through studies of electron microscopy and electrophysiology, it was possible to verify the recovery of the nerve structure and functionality, respectively. “Regeneration does not always imply functional recovery. In this case, yes, responses to stimuli are obtained. We were able to prove that it recovers part of its functionality”, highlights Soto. “What is achieved is a remyelination process, that is, the myelin, a specialized membrane that facilitates the speed of conduction of nerve impulses, is recovered. When there is an injury, the nerve demyelinates”.
Experts are enthusiastic about the idea that this technique can potentially be transferred to an adult population and emphasize that it is applicable to any peripheral nerve. “In the central nervous system it would be more difficult. The transplanted cells could arrive and exert their effect, but it would be more complex to get their direction through an external magnet. The location of the sciatic nerve makes it more accessible to external magnetic forces”, concludes Setton-Avruj.