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| The study is led by Professor Daniel Tornero and researcher Alba Ortega , from the Faculty of Medicine and Health Sciences and the Institute of Neurosciences of the University of Barcelona Photo Credit: Courtesy of University of Barcelona |
The brain’s mechanisms for repairing injuries caused by trauma or degenerative diseases are not yet known in detail. Now, a study by the University of Barcelona describes a new strategy based on stem cell therapy that could enhance neuronal regeneration and neuroplasticity when this vital organ is damaged. The results reveal that the use of brain-derived neurotrophic factor (BDNF), combined with stem cell-based cell therapies, could help in the treatment of neurodegenerative diseases or brain injuries.
Combining cell therapy with BDNF production
BDNF is a protein that is synthesized mainly in the brain and plays a key role in neuronal development and synaptic plasticity. Several studies have described its potential to promote neuronal survival and growth, findings that are now extended by the new study.
“The findings indicate that BDNF can promote the maturation and increase the activity of neurons generated in the laboratory from donor skin cells. The skin cells must first be reprogrammed to become induced pluripotent stem cells (iPSCs), and then differentiated to obtain neuronal cultures,” says Daniel Tornero, from the UB’s Department of Biomedicine and the CIBER Area for the Neurodegenerative Diseases (CIBERNED).
In this way, the study combines cell therapy with the production of BDNF in the same cells. This study confirms the beneficial effects of this growth factor in neuronal cultures derived from human stem cells, the same cells that are used in cell therapy to treat, for example, stroke in animal models.
“This strategy is being applied at an experimental level to design cell therapies and to generate laboratory models to help study brain diseases,” says Tornero. When these neural progenitor cells (NPCs) are modified to continuously overexpress the BDNF protein, “we obtain more mature and active neuronal cultures, without altering the normal organization of their connections or the functional networks,” explains researcher Alba Ortega.
The study focuses on the more functional aspects of neuronal regeneration, such as neuronal activity and axon generation, which are directly involved in the integration of cells that are transplanted into the brain.
“In addition, cells that produce BDNF are able to attract axons — the extensions that allow communication between neurons — more efficiently. This chemo-attraction effect would be related to the production of this factor,” says the researcher.
BDNF’s ability to attract growing axons has been described previously. Now, the team shows this effect for the first time in neurons derived from human stem cells using a microfluidic chip system. This innovative technology — with two chambers that isolate populations of neurons with or without the ability to produce BDNF — makes it possible to grow populations of neurons communicating through small channels and thus observe precisely how they interact with each other.
“The cells that produce BDNF generate a concentration gradient in these channels, which we believe guides and facilitates the formation of neuronal projections in a specific direction,” says student Santiago Ramos, representing the group of students who have contributed an innovative perspective to the conceptual and experimental design of the study.
Complementing the brain’s natural ability to regenerate itself
Neurodegenerative diseases and neuronal injuries, which are increasingly frequent in the population, are one of the major challenges for healthcare systems. As the endogenous regenerative capacity of the human brain is very limited, lesions only partially recover and affected patients are often left with motor and cognitive sequelae. In this context, there is an urgent need to design strategies that complement these endogenous brain mechanisms with human stem cell-based therapies to promote neuronal repair, functional integration and more efficient recovery.
In this regard, the team plans to transfer these results to animal models, a line of research developed for some time in this laboratory to improve human stem cell therapy in ischemic stroke lesions affecting the cerebral cortex.
The application of preclinical advances in patients will mark a turning point in the treatment of many neurodegenerative diseases. However, there are still many obstacles to implementing stem cell-based therapies and avoiding potential side effects (tumor generation, etc.). Some international clinical trials based on stem cell transplantation for the treatment of patients with Parkinson’s disease (in Japan, Sweden and the United States) are showing promising results.
“Although there are many challenges, progress in Parkinson’s clinical trials shows that we are closer than ever to applying these therapies safely in patients with stroke or other neurodegenerative diseases,” the experts conclude.
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| The participation of the group of UB students awarded one of the gold medals of the iGEM 2024 international synthetic biology competition has been decisive in the research. From left to right, Santiago Ramos, Luna Goulet, Marc Magem, Alba Cartró, Ares Font, Andrea Camí, Sergi Fornós, Jaume Ros, Marc Fabrellas, Irene Agudo, Emma Esquirol, Àlex Roger and Laila Olivella. Photo Credit: Courtesy of University of Barcelona |
The study, published in International Journal of Molecular Sciences, is led by Professor Daniel Tornero and researcher Alba Ortega, from the Faculty of Medicine and Health Sciences and the Institute of Neurosciences of the University of Barcelona (UBneuro). The study involves the decisive participation of a group of UB students who were awarded one of the gold medals in the international synthetic biology competition iGEM 2024, the most important international synthetic biology competition for young researchers.
Authors: Alba Ortega-Gasco, Francesca Percopo, Ares Font-Guixe, Santiago Ramos-Bartolome, Andrea Cami-Bonet, Marc Magem-Planas, Marc Fabrellas-Monsech, Emma Esquirol-Albala, Luna Goulet, Sergi Fornos-Zapater, Ainhoa Arcas-Marquez, Anna-Christina Haeb, Claudia Gomez-Bravo, Clelia Introna, Josep M. Canals, and Daniel Tornero
Source/Credit: University of Barcelona
Reference Number: mols101425_01
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