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Luisa DiPietro Discovers Healing Skin's Secrets

Luisa DiPietro. Credit: Jenny Fontaine.

AAAS Fellow Luisa DiPietro wants to unlock one of the body's most intriguing secrets, the mechanism of perfect healing.

Wounds in the mouth heal without a scar, and new blood vessels that arise around an oral wound develop and perfuse with an efficiency not seen in the skin, said DiPietro, director of the Center for Wound Healing & Tissue Regeneration of the University of Illinois at Chicago (UIC) and a professor or periodontics in UIC's College of Dentistry.

"There's definitely something very different about the oral cavity and its response to injury. It heals really well, and quickly. There's less over-exuberant repair, which is what happens in the skin," she said.

DiPietro's lab has been a leader in exploring the mechanisms of healing in oral mucosa, the type of tissue in the mouth — how new blood vessels form there after an injury, a process known as angiogenesis; the role inflammation plays in healing; and some aspects of the genomic regulation of wound repair. "If you look at the number of genes that get turned on and off, it's about half as many in the oral cavity as for the same-sized injury to the skin."

DiPietro's research leads her to believe that a few processes that occur normally in the skin actually promote scarring after injury. Her hope is to devise treatments that will allow skin to heal seamlessly.

"One of the first things we found was less inflammation in oral mucosal wounds than in the skin," she said. Researchers had already demonstrated that fetal repairs, which also scar very little, had minimal inflammation. However, without at least a modicum of white blood cells going after bacteria that invade a skin wound, "you're going to get infection. Some inflammation is definitely necessary," DiPietro said.

Why doesn't that hold true in the mouth, which has plenty of microbes that could cause infection? DiPietro said, "We think it's because there are defensins there that prevent infection. You can get away with much less inflammation in the mouth." The oral cavity also has fewer mast cells, a type of white blood cell that promotes inflammation. Saliva may also play a role; it has growth factors. Angiogenesis is another variable. DiPietro's team is looking at blood-vessel formation in human scars.

"All the surgical textbooks say angiogenesis is necessary," DiPietro said, but in healing skin, her team saw too many vessels develop, including abnormal ones that didn't do a good job of perfusing — delivering blood to the capillaries. "They don't even provide very good oxygenation," she said.        

During healing, "in the oral mucosa, vessels grow just to the right level and stop. They mature more quickly and provide great perfusion," DiPietro said. There are fewer vessels in the mouth, "but they're more mature and they're better arborized" — with a desirable branching, tree-like appearance. "They're in an arrangement that provides great oxygenation."

Anna Szpaderska, then a postdoc in DiPietro's lab, developed the mouse model the team used to study the oral mucosa, Pietro said. "If you reduce the number of vessels by about half, and put in factors that tell them to mature faster, so you get that enhanced oxygenation, the wounds will heal with less scar formation in the skin. We've seen that in a mouse model, and other people have reported it in other models."

In humans, she said, "there are a few studies from the Netherlands that show that more angiogenesis actually predicts a hypertrophic scar" (an unusual, unsightly type).

DiPietro is excited about the prospect of extending perfect wound healing in humans, but she thinks it's going to take five years or so to get to that point. Her team is trying their methods in a rabbit model now. "It's going to be a lot more challenging in people," she said.

DiPietro was one of four children growing up in Charleston, Illinois, a college town in the middle of the state. Her father was a math professor who "would constantly give us puzzles or logic games. He encouraged us to think analytically. My mother was a librarian. She was the one who encouraged us to be inquisitive. I think we all have a great appreciation for that upbringing, a place where we were allowed to think very critically, to question things without any fear," she said.

So DiPietro was a natural for research. But at 19, she was in a terrible bike accident. "I broke a whole bunch of front teeth and smashed up the side of my face. I was very devastated. I felt disfigured, but I healed, right? I healed. I had a great dentist, he restored my teeth, and everything was fine,” she recalled.

Her appreciation for the restorative possibilities of dentistry played a major role in her initial choice of a career, DiPietro said. She was a full-fledged dentist before she finally admitted to herself that "I was not going to be satisfied unless I did research."

She got a PhD in immunology and worked in the lab of AAAS member Peter Polverini then at Northwestern University Medicine and Dental Schools. "He was looking at all these cell types, especially the macrophages, a type of white cell, and how they could promote tissue growth," she recalled.

DiPietro “re-engineered” herself to work in the area of wound healing; she hasn't practiced dentistry for years. Of her research, she said, "I just love it."

She said, "First of all, it's essential. If you can't heal, that's incompatible with life. But healing is really complicated. It's at the intersection of a lot of processes; it's linked with developmental processes. That gives you a lot of room to investigate, and continue to move the field forward."


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<p>Luisa DiPietro. Credit: Jenny Fontaine.</p>
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