Harvard stem cell biologists announced on Mar. 24 that they have found a way to potentially regrow wounded skin without scarring, based on new research conducted in mice.
The study, published in Cell on March 20, outlines how scientists were able to unblock an embryonic healing mechanism that normally shuts down after birth. This discovery could lead to future therapies for human patients who suffer from scars following injury.
“Essentially, we found a way to make the wound healing outcome a lot better by learning how embryos do this so well,” said Ya-Chieh Hsu, professor of stem cell and regenerative biology at Harvard and senior author of the study. “I’m excited because we pushed the needle in a really important direction. When we have a wound, most skin cell types cannot regenerate, and we get a scar. But now I think we’ve found a way to change that, so that many cell types can regenerate, and we don’t get a scar.”
The researchers discovered that while embryonic wounds heal without leaving scars by restoring all types of skin cells, this ability fades soon after birth. Their experiments showed that postnatal wounds attract excessive nerves due to increased activity of the gene Cxcl12 in fibroblasts—a process called hyperinnervation—which prevents regeneration of other key skin cells.
By depleting Cxcl12 or blocking nerve signaling with botulinum toxin A (Botox), the team was able to restore diverse cell regrowth in mouse skin after injury. Lead author Hannah Tam said her team initially assumed immune cells played the main role but later realized it was actually fibroblast-nerve interactions blocking regeneration: “The surprising part is that we identify a block,” Tam said. “And this block is through fibroblast-nerve interaction… I feel that this is very helpful to the field because now we can really consider these two as actual communicators.” Hsu added: “I didn’t think that we’d have to retract a brake, which actually is good news — it’s a lot easier… It gives me hope that this might be applicable to improving wound healing in humans.”
This research was supported by federal funding from the National Institutes of Health.
