University of Barcelona Unveils Breakthrough Strategy for Brain Regeneration

Brain regeneration after injury or neurodegenerative disease remains one of the greatest challenges in modern medicine. Despite advances in neuroscience, the mechanisms of neuronal repair and synaptic plasticity remain poorly understood.

A new study led by the University of Barcelona proposes an innovative strategy based on the combination of cell therapies with the sustained administration of brain-derived neurotrophic factor (BDNF), with the aim of promoting neuronal maturation, functional connectivity, and the integration of transplanted cells into damaged brain tissue.

The work, published in the International Journal of Molecular Sciences, was developed by researchers from the Institute of Neurosciences at the University of Barcelona (UBneuro) and the Faculty of Medicine and Health Sciences. The research proposes an approach that combines cell therapy with genetic bioengineering to enhance central nervous system regeneration.

A dual strategy to repair the brain

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, along with traumatic brain injuries and stroke, represent a growing burden on healthcare systems worldwide. These pathologies cause the irreversible loss of neurons and synaptic connections, resulting in cognitive, motor, and behavioral impairment. Since the human brain’s natural ability to regenerate is limited, biomedical research seeks to develop therapies that can replace damaged cells and restore lost neuronal function.

In this context, stem cell therapies have emerged as one of the most promising lines of research. These cells possess the ability to differentiate into different neuronal types and establish new connections, opening up the possibility of regenerating damaged brain circuits. However, one of the main obstacles remains the functional integration of transplanted cells and their long-term survival in the injured brain environment.

The University of Barcelona team addressed this challenge using a strategy that combines the use of induced pluripotent stem cells (iPSCs) —reprogrammed from human skin cells— with the continuous expression of BDNF , a key protein in the development and maintenance of the nervous system. BDNF promotes neuronal survival, stimulates axonal growth, and enhances synaptic plasticity, all of which are essential for the brain’s functional recovery after injury.

Improve neuronal maturation and connectivity

The researchers generated cultures of human neural progenitor cells genetically modified to overexpress BDNF, observing a significant increase in neuronal maturation and synaptic activity. This effect was accompanied by a greater number of mature neurons without altering the organization of neuronal networks , suggesting that the protein stimulates cellular function without inducing structural alterations.

The study also revealed that cells that produce BDNF have the ability to attract the axons of other neurons, a phenomenon known as chemoattraction. This finding was confirmed using microfluidic chips, a technology that allows neuronal populations separated by microchannels to be cultured and how they communicate analyzed. The results showed that axons preferentially gravitate toward regions with higher BDNF concentrations, which could facilitate the integration of neuronal transplants into the recipient brain.

These observations are relevant because the precise orientation and connection of transplanted axons is essential for restoring functional neuronal circuits. The study suggests that the sustained secretion of BDNF by transplanted cells could act as a natural chemical guide, improving connectivity between new and existing neurons in brain tissue.

Although the results are preliminary and obtained in laboratory models, the authors highlight the potential of this strategy for application in neurodegenerative diseases or brain injuries in animal models. Specifically, the research group has been working for years on cell therapies for ischemic stroke, a condition that causes severe damage to the cerebral cortex and leaves persistent motor and cognitive sequelae.

The findings also contribute to overcoming some historical limitations of stem cell therapies. In ongoing clinical trials for Parkinson’s disease, for example, it has been shown that dopaminergic cells derived from human pluripotent stem cells can integrate into patients’ brains and improve motor symptoms. However, efficacy varies, and functional integration is not always achieved. Incorporating neurotrophic factors such as BDNF into the design of these therapies could increase cell survival and the quality of established connections.

The research also suggests that controlled BDNF expression does not interfere with the formation of stable neuronal networks, avoiding the risk of hyperexcitability or disorganized connections. This balance is crucial to ensuring the functionality and safety of neuronal transplant-based therapies.

Future prospects for brain regeneration

The next step will be to validate these results in animal models to determine whether the improvements observed in vitro can be translated into measurable functional benefits , such as motor or cognitive recovery after brain injury. This preclinical phase will be crucial for evaluating the feasibility of using genetically modified neural progenitor cells in cell replacement therapies.

In the long term, the goal is to develop personalized treatments that combine the precision of cellular engineering with the brain’s own reparative capacity. This integrated approach could mark a turning point in the treatment of diseases that currently have no cure and open up new opportunities in neurorehabilitation and regenerative medicine.

Recent advances in gene editing, tissue bioengineering, and translational neuroscience make it possible to imagine a future in which neuronal regeneration ceases to be a theoretical concept and becomes a clinical reality. The combination of human stem cells with controlled BDNF production is emerging as one of the most promising avenues for restoring lost brain function and improving the quality of life for millions of people affected by neurological disorders worldwide.

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First published in GACETA MEDICA. A third-party contributor translated and adapted the article from the original. In case of discrepancy, the original will prevail.

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