A severed spinal chord is a devastating and potentially fatal injury for humans, and the idea that the body could heal itself seems like science fiction. The zebrafish, however, can indeed heal itself after such an injury.
With such a remarkable ability, scientists simply had to investigate the process that allowed the fish to perform the feat.
Duke University scientists have pinpointed a particular protein needed for spinal cord repair, and their study, published n the journal Science, could lead to major advances in tissue repair in humans.
Amazing Powers of Regeneration
This is one of nature’s most remarkable feats of regeneration,” said study senior investigator Kenneth Poss, professor of cell biology and director of the Regeneration Next initiative at Duke. “Given the limited number of successful therapies available today for repairing lost tissues, we need to look to animals like zebrafish for new clues about how to stimulate regeneration.”
The key for the team was to examine what genes’ activity changed after an injury. Dozens were strongly activated by injury, but one called CTGF (connective tissue growth factor) was of great interest.
Incredibly, when zebrafish suffer severed spinal chords a bridge is formed by cells projecting tens of times their own length across the gulf. Nerve cells follow over the next eight weeks or so until the gaps are filled and the injury is reversed.
Rising levels of CTGF were found in the supporting cells, or glia, that form the bridge.
“We were surprised that it was expressed in only a fraction of glial cells after the injury. We thought that these glial cells and this gene must be important,” said lead author Mayssa Mokalled, a postdoctoral fellow in Poss’s team.
They were so important, in fact, that when the researchers tried deleting CTGF genetically, regeneration in the relevant fish did not occur.
Humans’ genetic similarities with fish
Humans and zebrafish share most protein-coding genes, including CTGF. The human CTGF protein is around 90 percent similar in its amino acid building blocks to the zebrafish form, and the addition of the human version of CTGF to the injury site in fish aided regeneration. The team showed that fish recovered just as efficiently with this method.
“The fish go from paralyzed to swimming in the tank. The effect of the protein is striking,” Mokalled said.
This does not, at this stage, mean that CTGF works as efficiently in humans with such a severe injury, partly because of the formation of scar tissue.
Research on mammals will need to take place, and Poss explained that what may be crucial is how the protein is controlled rather than its make-up.
“I don’t think CTGF is the complete answer, but it’s a great thing to have in hand to inform new ways to think about the real challenge of trying to improve regeneration,” Poss concluded.
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