Facial wound fibroblasts shown to reduce scarring in other areas of the body

Drs. Michael Longaker (L), Derrick Wan (C), and Dayan Li (R). Image courtesy Stanford Medicine News

Facial wounds may hold the key to minimizing scarring, according to new preclinical research that studied why the face heals differently than the trunk and extremities. The findings, published Jan. 22, 2026, in Cell, outline a neural crest–derived fibroblast program and a ROBO2–EP300 signalling pathway that together drive a more regenerative, less-fibrotic pattern of repair.​

Scarring is a major source of morbidity, extending far beyond cosmetic concern. Fibrotic remodelling can impair organ function and contribute to chronic pain, disease, and death—roughly 45% of deaths in the United States are linked to some form of fibrosis, often in the lungs, liver, or heart. Cutaneous scars, while rarely fatal, are mechanically stiff, structurally weak and devoid of adnexal structures, limiting thermoregulation. Clinicians have long recognized that facial wounds typically heal with less conspicuous scarring than those on the torso or extremities.

Using mouse models, investigators from Stanford Medicine created standardized full-thickness skin wounds on the face, scalp, back, and abdomen, controlling for mechanical forces with sutured plastic rings and providing analgesia during healing. After 14 days, facial and scalp wounds showed lower expression of proteins associated with scar formation and smaller scar size than back or abdominal wounds.

The team then isolated fibroblasts from each site and injected them into the backs of control mice. Fibroblasts derived from facial skin reduced expression of scarring-associated proteins at the recipient site compared with fibroblasts from the scalp, back, or abdomen.

“We found you don’t need to change or manipulate all fibroblasts within the tissue to have a positive outcome,” said Dayan Li, MD, PhD in a press release. “When we injected fibroblasts that we had genetically altered to more closely resemble facial fibroblasts, we saw that the back incisions healed very much like facial incisions, with reduced scarring, even when the transplanted fibroblasts made up only 10 to 15 per cent of the total number of surrounding fibroblasts. Changing just a few cells can trigger a cascade of events that can cause big changes in healing.”

“Now that we understand this pathway and the implications of the differences among fibroblasts that arise from different types of stem cells, we may be able to improve wound healing after surgeries or trauma,” added co-senior author Dr. Derrick Wan of Stanford Medicine.

Dr. Michael Longaker from Stanford, also a co-author, noted that the mechanisms are likely relevant to internal organs as well. “There’s not a million ways to form a scar,” he said. “This and previous other findings in my lab suggest there are common mechanisms and culprits regardless of the tissue type, and they strongly suggest there is a unifying way to treat or prevent scarring.”