Researchers have uncovered new details about how some fish can regenerate their tail after an injury, which could inch us closer to employing regenerative medicine in people.
“Humans have all the components to regenerate, but we don’t do it,” says at the Stowers Institute for Medical Research in Missouri. “There’s something missing, and we believe that the missing part, it’s a regulation part.”
One mystery about animal regeneration is how the body calculates the extent of the repair needed – whether it needs to grow back just the tip of a tail, for instance, or the tail in its entirety. To find out more, Granillo’s team sliced off the end of the tail fins of African turquoise killifish (Nothobranchius furzeri) and tracked the response of their genes and cells.
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When a bit of the tail fin is chopped off, cells at the tip of all the fish’s fins – even those that aren’t damaged – respond and activate genes in charge of regeneration. The cells in the healthy fins quickly settle down and return to their original, relaxed state. But those in the damaged tail fin keep their regeneration genes activated, which then send out a call for help to a class of first responder cells called progenitor cells. These are located in the tissues left in the tail fin, such as bones, nerves and muscles, and then migrate to the bleeding edge of the injury and quickly reproduce to create what is needed.
“Regeneration doesn’t invent a new cell. It’s something that already exists,” says Granillo.
While this migration process is occurring, skin cells have already begun to grow and wrap around the injury to protect the wound, and these cells remake the layer of proteins and sugar that usually separates the skin from the underlying tissue – a padding called the extracellular matrix.
The research team say that the extracellular matrix is then used like an emergency notice board on which the immune system can essentially pin signals to provide information to the progenitor cells and direct them in the rebuilding process. “It creates [a] reservoir of signals that will relay the information to the [progenitor] cells,” says Granillo.
These signals dictate how many progenitor cells are needed to make the repair and where in the body they should be recruited from. What’s more, the new analysis suggests that the signals also tell the progenitor cells how long they need to stick around to carry out the job. The more significant the damage, the longer they need to linger.
Prior research had shown that regeneration is faster when more tissue is missing and slower when the damage isn’t as bad, but it was unclear why. So Granillo’s team used the CRISPR-Cas9 gene editing technique to remove sqstm1, one of the genes thought to tell the progenitor cells how quickly to repair damage. Without the gene, the tissue grew back quickly even when the damage was minor.
This suggests that the regeneration process typically triggers fast regrowth, but if the body recognises that the damage is relatively minor, the gene sqstm1 hits the brakes. Granillo and his colleagues hope to figure out why in future research.
This study helps us understand what information about the pattern and position of regrowth the remaining cells can remember after an amputation, says at Boston College, Massachusetts, who wasn’t involved in the research. She thinks it is a thoughtful and meticulous study that builds on previous work.
This is especially necessary for a better grasp of why regeneration happens in some animals but is absent in others, including humans, says team member , also at the Stowers Institute for Medical Research. However, it may still be too soon to speculate on how we can best use this knowledge to advance therapeutic interventions in humans, he says.
“If we can solve this puzzle, we will have access to regeneration in humans,” says Granillo. “And regeneration in humans will change humanity.”
iScience
