Will damaged skin one day be able to completely regenerate without leaving a scar?
A new study by stem cell biologists at Harvard University was published on March 20th. cell We have uncovered a way to completely regenerate skin by unblocking the fetal healing mechanism, which stops after birth. This study, demonstrated in mice, suggests a potential avenue to develop similar treatments in human patients.
“Essentially, we discovered a way to make wound healing outcomes much better by learning how embryos do well at wound healing,” said Ya-Chieh Hsu, professor of stem cell and regenerative biology and principal faculty member at Harvard’s Stem Cell Institute and senior author of the new study. “We’re excited because we’ve advanced the needle in a very important direction. When you have a scar, most types of skin cells can’t regenerate and you’re left with a scar. But now we think we’ve found a way to change that so that many types of cells can regenerate and you don’t leave a scar.”
The skin is often touted as a prime example of an organ that can regenerate itself. The truth is, healing is not completely skin deep.
After injury, epidermal stem cells reseal the surface and fibroblasts deposit dense collagen scar tissue. But the skin also contains a range of other cells (10 to 50 types, depending on how they are classified), including hair follicles, blood and lymph vessels, sweat glands, pigment cells, immune cells, fat cells, and nerves. Most of these other types fail to regenerate, leaving scarred skin fundamentally altered.
Previous research has shown that fetal wounds can heal without scarring, but new research reveals more. After injury, fetal skin recovers all cell types, but this ability declines soon after birth. This study reveals the molecular mechanism behind this switch and how it can be turned back on.
“Our findings suggest that some organs retain an inherent regenerative capacity that is simply suppressed, and removing this block may be sufficient for regeneration to occur,” Professor Hsu said. “In other words, regeneration may not need to build anew, but simply release.”
This new discovery is the culmination of five years of research by lead author Hannah Tam, Ph.D., 26, a graduate of the Harvard Kenneth C. Griffin Graduate School of Arts and Sciences in the Biology and Biomedical Sciences Program at Harvard Medical School. She learned how to perform microsurgery on tiny mouse fetuses and newborn babies under a dissecting microscope.
To investigate wound healing, Tam used a biopsy punch tool to remove full-thickness sections of skin and compared how organs regenerated in fetal and postnatal mice at several time points.
One of the challenges was tracking the fetal wound’s location, since it had healed so completely that it was indistinguishable from normal skin. The scientists marked the injury site with fluorescent beads and henna ink.
They found that the ability to regenerate skin steadily declines during the first few days of life. The most dramatic changes occurred between 3 days before birth and 5 days after birth, a period of only 8 days.
The skin of mice that were wounded three days before birth regenerated different types of cells and looked very similar to unwounded skin. However, after the injury occurred five days after birth, the area became covered with epithelial cells, filled with collagen scar tissue and an abnormally dense density of nerve fibers and immune cells. Many other types of skin cells could not regenerate.
The team then sought to identify the key factors behind these differences in regeneration.
They discovered that nerves were densely packed at the site of the postnatal wound. This “hyperinnervation” occurs because fibroblasts in the postnatal wound upregulate genes. Cxcl12It recruits excess nerves to the injured area and prevents the regeneration of other types of skin cells.
When researchers run out Cxcl12 In the mice’s postnatal wounds, “hyperinnervation” was suppressed and the skin regenerated different types of cells. Blocking local nerve signaling with botulinum toxin A (Botox) had a similar effect.
Tam said the research team “hit a wall” midway through their research, believing that immune cells were somehow involved in the regeneration process. A breakthrough occurred when we discovered that the real disorder was the signaling behind the hyperinnervation and that we could turn it off and restore full regeneration of the skin.
“The amazing thing is that we identified the blocks,” said Tam, now a postdoctoral researcher at the Scripps Research Institute in California. “And this block is done through the interaction of fibroblasts and nerves. The relationship between these two different cell types has not been a focus in wound healing research. We feel this will be very helpful to the field, because now we can think of these two as actual messengers.”
Before the study, Hsu had predicted that the key to wound healing was recreating a set of “pro-regenerative factors” that mimic fetal healing. The solution turned out to be much simpler.
“I didn’t feel like I had to put the brakes back on, which is actually good news. It’s a lot easier,” she said. “It gave us hope that this might have applications in improving wound healing in humans.”
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Reference magazines:
Therefore, H.T. Others. (2026). Hyperinnervation inhibits organ-level regeneration in mammalian skin. cell. DOI: 10.1016/j.cell.2026.02.027. https://www.cell.com/cell/fulltext/S0092-8674(26)00234-5
