·
·
Tech & Science
Scientists at the University of Cambridge reversed nerve fiber damage by blocking a genetic brake, enabling regrowth in lab-grown human brain and spinal cord tissues.
Researchers at the University of Cambridge have successfully reversed a biological mechanism that inhibits nerve repair by using lab-grown human brain and spinal cord tissues. This breakthrough restored the ability of damaged nerve fibers to regrow, challenging the long-held belief that such nerve damage is permanent.
The team developed miniature brain and spinal cord circuits in vitro that replicate the neural pathways controlling movement. Through this model, they found that damage to these neural connections may be reversible, despite previous assumptions of permanence.
In 2021, Dr. András Lakatos and his colleagues at Cambridge created small brain-like organoids from human patient-derived stem cells. These stem cells were directed to form three-dimensional structures resembling parts of the human cerebral cortex. The initial organoids helped identify molecular abnormalities in motor neurone disease and test potential interventions.
Expanding on this work, the researchers engineered a miniature system connecting brain and spinal cord organoids. Since these structures are separate in the human body but linked by axons, the team grew them independently and observed nerve fibers extending from brain tissue to spinal cord tissue. This neural circuit was functional enough to induce contractions in small muscle cell clusters.
The miniature nervous systems were maintained in the lab for over a year. The experiments showed that neurons could regrow damaged axons up to about day 150 of development, corresponding to mid-pregnancy stages. Beyond this point, the neurons’ regenerative capacity declined sharply.
George Gibbons, the study’s first author, explained that neurons from less mature organoids regrew long fibers after injury, whereas those from more mature organoids exhibited a significant decrease in regrowth ability. He stated, “Poor regeneration is built into human neurons as they mature in the central nervous system.”
To investigate the cause, the researchers analyzed gene activity in neurons connecting brain and spinal cord. They identified a gene network acting as a biological switch that limits axon growth as neurons mature and form synapses. Blocking key regulators in this network restored the neurons’ capacity to extend axons.
The team screened a drug database for compounds affecting this gene network and identified lynestrenol, a hormone drug approved for menstrual disorders and contraception. Applying lynestrenol to damaged neurons significantly increased axon regrowth.
Although scar tissue and inflammation also hinder nerve repair after injury, the researchers emphasized the importance of understanding neuron-specific barriers. Evidence suggests younger neurons can extend axons even in hostile injury environments.
Dr. Lakatos, the project’s senior author, noted, “The nerve fibers carrying movement signals rarely regrow after brain and spinal cord damage, making paralysis usually permanent. Our model indicates this regenerative block occurs during development but can be reversed. While lynestrenol may not be the final treatment, it demonstrates the potential to target human neurons directly for axon regeneration.”
Organoids, or “mini organs,” are increasingly valuable for studying human biology and disease. While animal models remain important, differences between their nervous systems and humans limit translational relevance. Human organoids provide closer biological representation, enabling investigation of diseases and treatments difficult to model in animals.
Dr. Lakatos added that much knowledge about nerve regeneration comes from rodent studies, whose neurons behave differently from human neurons. The organoid models help bridge this gap and contribute to reducing animal use in research.
At Cambridge, organoids are also used in diverse applications such as liver repair, studying Crohn’s disease in children, and examining early pregnancy stages.
