“A new pandemic,” warns Claudia Banchio, a council researcher and group leader at the Institute of Molecular and Cellular Biology of Rosario (IBR, CONICET-UNR), when she indicates that by 2050 it is estimated that the incidence of diseases such as Alzheimer’s and Parkinson’s would reach 150 million cases worldwide. These disorders share a common event that is the death of neurons, the functional cells of the brain, which generates cognitive impairments that constitute the first cause of disability and the second cause of mortality in people over 65 years of age. The loss of neurons is irreversible in principle because they are cells that cannot multiply.
“While this is true, we now know that neurons can be regenerated from stem cells,” says Banchio, and explains that in the brain there are neural stem cells that have the ability to differentiate into neurons, replacing those that can die throughout life. “However, in an adult brain they are scarce and insufficient to completely repair the damage, and that is why these diseases are suffered,” he adds.
This fact fuels the intense search for an effective way to increase neural stem cells in the brain. In pre-clinical studies, stem cell transplantation has been evaluated as an alternative, although showing not very encouraging results. This fact fuels the intense search for an effective way to increase neural stem cells in the brain. In pre-clinical studies, stem cell transplantation has been evaluated as an alternative, although showing not very encouraging results. This fact fuels the intense search for an effective way to increase neural stem cells in the brain. In pre-clinical studies, stem cell transplantation has been evaluated as an alternative, although showing not very encouraging results.
A new investigation conducted by Banchio makes a valuable contribution to this search by demonstrating that the extracellular vesicles manufactured and released by neural stem cells in the brain have two fundamental effects: on the one hand, they favor the proliferation of other stem cells and, on the other In part, they induce them to differentiate into functional neurons.
“We think that these vesicles –called exosomes- could be efficient in acting on the stem cells that are in the brain, making them proliferate and also differentiate into new neurons”, he emphasizes. Susana Delgado, CONICET doctoral fellow who carried out her thesis with this research work published in the journal Frontiers in Molecular Neuroscience, adds that they also observed how the exosomes “recover the normal functionality of damaged neurons or with aberrant morphologies that can be produced by an inflammatory situation in the brain.”
The experiments that yield these remarkable results were carried out using stem cells isolated from the brain of mice at thirteen days of gestation.
“We start with mouse embryos that measure more or less one centimeter”, explains Delgado, the first author of the work, adding: “From there we obtain the stem cells to carry out the experiments, it is very precise work and many hours under the microscope fluorescence, which are the most beautiful”.
Through cell biology techniques that combine the use of antibodies with molecules that emit fluorescence, specific structures present in different cell types can be identified and made visible, which would otherwise be seen translucent when viewed under a microscope.
“In this way, we were able to verify that the promoting effect of exosomes on the differentiation of stem cells generates neurons and not another type of nerve cell,” explains Delgado.
The scientific basis of a startup
Due to its novelty and inventiveness, the results of this research are protected by a provisional patent and are the basis of a startup that seeks solutions for neurodegenerative diseases called EXO+.
“The fact that these extracellular vesicles induce stem cell differentiation into functional neurons and that they increase the parameters associated with neuronal function that are generally affected by neurodegenerative diseases, raises the hypothesis that they could be used to regenerate neurons in the context of these pathologies” , anticipates Banchio.
When a startup arises from the research carried out by CONICET scientists in its executing units, the organization has a leading role in the development of the company, which is called a Technology-Based Company (EBT), since it has the capacity to generate and transfer technology, this being the basis of its competitive advantage and its business activity. In the case of EXO+, the impetus provided by the SF500 investment committee, an initiative of Bioceres SA and the Province of Santa Fe that seeks to promote interactions between the scientific system and the productive sector, also stands out.
Banchio highlights the importance of this technological link because “without basic science, something applied cannot be achieved”, and clarifies that the research they continue to do is the same “but tries to validate the use of this knowledge faster”. “In Argentina, researchers are still not used to doing these startups, but the reality is that the science that creates them can come out of the doctoral theses that we direct, as was the case in my case,” he emphasizes.
much to do
In the paths of research, the results always enable new questions. Currently, Banchio and his team have begun a series of biochemical analyzes to determine which of the molecules that make up exosomes are specifically those involved in promoting neuronal regeneration and to elucidate the molecular mechanisms by which they exert this effect on cells.
Also, Banchio advances: “We are interested in establishing whether exosomes are functional on human neurons under in vitro conditions that reproduce the effects of Parkinson’s and Alzheimer’s disease.” According to him, they also plan to carry out tests using “aged” stem cells and explains that this would allow us to see how they respond to exosomes from “younger” cells.
Undoubtedly, there is still a lot of work to be done in the laboratory, but the researcher’s enthusiasm flares when she looks to the future and declares: “We have come this far because I am convinced that this basic science cannot only be written in books or in magazines. scientific, but it has to reach society”.