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Stanford researchers investigate source of scarring

2570500512_22e7fdcd48_zIf you've ever had a piercing that you've let grow closed, you'll know that the healing process isn't perfect. There's almost always a little dimple to remind you of that perhaps questionable choice you may (or may not) have made during early adulthood.

Now former Stanford pediatric dermatologist Thomas Leung, MD, PhD, and developmental biologist Seung Kim, MD, PhD, have published some interesting research in Genes and Development regarding the healing and scarring process. Their findings may one day lead to advances in regenerative medicine.

As Leung, who is now an assistant professor at the University of Pennsylvania's Perelman School of Medicine explained in an email to me:

One of the great mysteries in biology is how salamanders and worms regenerate lost body parts following trauma. In contrast to wound healing, tissue regeneration restores tissue to their original architecture and function, without a scar.  Although less dramatic, a few examples of mammalian tissue regeneration exist, including liver and digit tip regeneration.  These examples suggest that the underlying mechanisms driving tissue regeneration may still be intact in humans and perhaps we may use them for regenerative medicine.

The researchers studied how the ears of mice heal from a hole punched through the thin tissue (much like  ear piercing in humans). In many strains of mice, the holes partially fill but remain visible. In a few others, the holes heal with little perceptible scarring. Leung and Kim found that the strains of mice that heal well lack production of a protein that normally recruits white blood cells to the injury; blocking the ability of the protein, called Sdf1, to signal to the white blood cells resulted in enhanced tissue regeneration and less scarring in mice that would normally have been unable to close the hole.

Because the drug used to block Sdf1 signalling is already used clinically in humans for another purpose, Leung is hopeful that it can quickly be tested in humans struggling to heal  chronic or slow-healing wounds. He is currently designing a clinical trial to test the drug, called AMD3100.

The implications of improved wound healing with less scarring stand to benefit many more people than just those wishing away the physical evidence of a hasty cosmetic decision. Tens of millions of surgical incisions are made every year, and not all heal well. Scar tissue is less flexible than normal skin and can significantly interfere with function. In addition, people with certain medical conditions such as diabetes or poor circulation can face ongoing disability or amputation when wounds don't heal. But the group that inspired Leung to conduct the research is especially poignant.

As Leung explained:

 The inspiration for this work was driven by our clinical experience.  At Stanford, I co-directed the Epidermolysis Bullosa (EB) clinic.  EB is a rare genetic skin disease (about eight babies are affected per million births in this country), where affected patients lack a protein that binds the skin together, resulting in fragile skin. Incidental trauma like rubbing of skin against clothing tears the skin and leaves a scar.  This endless cycle of trauma and scarring and fibrosis inevitably leads to decreased joint function and complete loss of hand function by teenage years.

My recent article for Stanford Medicine magazine and the accompanying video shed light on this devastating condition. Even a small improvement in the pain these children suffer would be a tremendous step forward. And, although Kim emphasizes that greater feats in regenerative medicine (limb regeneration, anyone?) are still years of research away, this finding shows that we're making progress.

Previously: Limb regeneration mysteries revealed in Stanford studyTo boldly go into a scar-free future: Stanford researchers tackle wound healing and Life with epidermolysis bullosa: “Pain is my reality, pain is my normal”
Photo by The Guy with the Yellow Bike

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