Organ regeneration trigger uncovered
A signal that triggers tissues and organs to regenerate rather than form a scar has been uncovered by US scientists.
Many organisms, but notably not mammals, have the ability to regenerate entire organs and limbs if a body part is lost or damaged. Famously, salamanders can grow a new leg following an amputation.
The same injury sustained by a human, on the other hand, leads to irreversible loss of the body part.
Salamanders and similar species do this by possessing the ability to reactivate the genetic sequence that is executed during embryonic development to build tissues from scratch. This appears to be deactivated in more complex, longer-lived animals, possibly as a defense against cancer.
However, writing in Cell Stem Cell, Johns Hopkins researcher Luis Garza and his colleagues have found a chemical signalling system that appears to be capable of reanimating the developmental genetic programme to promote regeneration.
The team were working with two groups of mice, one of which showed very good regenerative effort in response to skin wounding, while the other healed poorly with chiefly scar tissue.
Samples from the healing tissue from both groups of mice were compared genetically to look for genes that were consistently turned on or off, or more strongly active in one group compared with the other. This highlighted a component of the immune response, called innate immunity, that detects hallmarks of viral infections, specifically the presence of a chemical called double stranded RNA.
However, careful probing showed that injured skin also produces double stranded RNA and activates this arm of the immune system, which, in turn, can turn on the regeneration process.
Boosting the activity of this signalling system, the team found, could turn their poorly-regenerating mice into better regenerators.
Genetic studies also confirmed that stem cells in the regenerating skin were being persuaded to adopt less specialised, stem-cell like forms capable of turning into, among other things, new hair follicles.
"What's amazing about this finding," explains Garza, "is that we've actually already been exploiting this pathway when patients go to the dermatologist and have dermabrasion or laser treatments to reduce the appearance of skin ageing. This damage is triggering the very same pathway."
According to Garza, the identification of this system means that such treatments might not be necessary in future, particularly since there are already drugs in development that can trigger the healing pathway.
Such a difference could make a major cosmetic difference to burns victims. "It might enable us to help people get back the normal hairs, which are absent from burned skin," says Garza.