Published: June 05, 2026, 13:58 UTC
When the spinal cord is damaged, the nerve fibers that carry movement signals from the brain rarely grow back. That is why paralysis after spinal cord injury is usually permanent. The neurons themselves do not die, but they lose the ability to extend their axons across the damaged site and reconnect with what lies beyond.
For decades, researchers have known that this regenerative capacity vanishes sometime during development, but the precise timing and the molecular switch that controls it have remained obscure. Most of what is known comes from rodents, whose neurons behave differently from human neurons.
A team at the University of Cambridge has now built a human model that bridges this gap. Using stem cell-derived organoids of the brain and spinal cord, grown separately and then connected across a gap to form what the researchers call a “connectoid,” they have identified when human central nervous system neurons lose their ability to regrow and, crucially, how to restore it.
The study was published May 26 in Cell Reports.
The Connectoid
The research team, led by Andras Lakatos and first author George Gibbons, grew cortical brain organoids and spinal cord organoids from human induced pluripotent stem cells. These were placed in separate compartments of a microfluidic device, allowing axons from the cortical organoids to extend across a channel and connect with the spinal cord tissue on the other side.
The system was functional. When the connected circuit was stimulated, it triggered contractions in co-cultured human muscle cells, demonstrating that the axons had formed working synapses with spinal targets.
By observing the connectoids at different stages of development, the researchers found that human CNS neurons retained a robust ability to regrow after injury until approximately day 150 of development. After that point, regenerative capacity dropped sharply. The timing corresponds roughly to mid-pregnancy in human gestational development.
“You cannot generalize from rodent studies to human spinal cord injury because human development takes much longer,” Lakatos said. “Our model provides a good indication that this block happens during development, and it can still be reversed after this point.”
The Genetic Switch
The team traced the loss of regenerative capacity to a gene-regulatory network that progressively limits axon growth as neurons mature and form synaptic connections. The network acts as a biological switch: once sufficient synaptic connections are established, the cell diverts resources away from axon growth machinery toward maintaining existing connections.
Blocking key regulators within this network using genetic tools allowed mature neurons to regain their axon growth capacity. But genetic intervention is not easily translatable to the clinic.
The researchers then screened a database of existing drugs for compounds that could influence the same gene network. They found lynestrenol, a progestogen hormone drug already approved for menstrual disorders and as a contraceptive. When applied to damaged human neurons in the connectoid model, lynestrenol significantly increased axon regrowth.
What It Does and Does Not Mean
The finding is a proof of concept that the intrinsic regenerative block in human CNS neurons can be reversed, even after it has been established. But Lakatos was careful to temper expectations.
“Lynestrenol itself may not be the answer to spinal cord repair,” he said. “But it shows us that, in principle, it should be possible to directly target human neurons and regenerate their axons.”
Several major caveats remain. The study was conducted entirely in vitro: the connectoid model does not include the scar tissue, inflammation, and chemical inhibitors that form at the site of a real spinal cord injury. Younger neurons can grow through such hostile environments, suggesting that solving the intrinsic growth block is a necessary first step, but not a complete solution.
More critically, restoring axon regrowth is not the same as restoring function. The regrown axons must re-establish appropriate, specific connections with the correct targets on the far side of the injury. Whether the strategy works in that context has not been tested.
The team is now working to validate these findings in animal models and to search for more effective drug candidates.
“Although we still need to show that this strategy will also help to re-establish appropriate connections between the brain and spinal cord cells,” Lakatos said, “this gives us hope that one day we may be able to treat conditions previously thought untreatable.”
Reference
Gibbons, G.M., Fuchsberger, T., Abdelgawad, M., Lakatos, A. et al. “A Human Corticospinal Organoid-Slice Connectoid Model Informs Enhancer Strategies for Post-Injury Axon Regrowth.” Cell Reports, Vol. 45, Issue 6, Article 117399 (2026). DOI: 10.1016/j.celrep.2026.117399