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Vol. LXIV, No. 8
April 13, 2012
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Tomic-Canic Explores Science of Wound-Healing

On the front page...

Dr. Andrew I. Dayton

Dr. Andrew I. Dayton

Normal human skin has a mind of its own. Wound it, even in the Petri dish, where you can grow massive sheets of it from a single biopsy, and it will start to heal itself.

But there is a population of patients, many elderly or with diabetes, whose wounds just don’t heed the chemical rallying cries of growth factors, cytokines and chemokines that instantly set to work once our protective covering has been breached.

In a talk she titled “Wizardry of Tissue Repair and Regeneration: A Tale of Skin Cells When Their Magic Is All But Gone,” Dr. Marjana Tomic-Canic, director of the Wound Healing and Regenerative Medicine Research Program at the University of Miami Miller School of Medicine, showed how cutting-edge science (no pun intended) is revealing more about the biology of skin, our largest organ.

Continued...

“We are now in the midst of an epidemic of chronic wounds,” she said at a Wednesday Afternoon Lecture on Mar. 7. According to 2005 data, worldwide, a lower limb is lost to diabetes every 30 seconds. In the United States, more than $25 billion is spent annually on wound care.

Tomic-Canic’s lab is exploring why some wounds don’t heal. “There are very few effective products,” she said, and wound-healing represents “a tremendous clinical burden.” While more than 3,000 products have been approved for treatment on the basis of safety, only a handful have reached the efficacy threshold for FDA approval, she said.

Tomic-Canic (l) speaks with NIH deputy director for intramural research Dr. Michael Gottesman at a reception in the NIH Library after her talk.

Tomic-Canic (l) speaks with NIH deputy director for intramural research Dr. Michael Gottesman at a reception in the NIH Library after her talk.

Photos: Michael Spencer

Tomic-Canic comes by her interest in skin honestly; she began her career as a pediatric nurse in a burn unit. “Skin has this enormous regenerative and proliferative potential,” she said. It is no surprise, she noted, that skin cells (fibroblasts) were the cell type to yield the world’s first induced pluripotent stem cells. Skin cells are robust and eager to do their job of maintaining a protective barrier to the outside world.

“These cells really do know what to do on their own, without our help,” Tomic-Canic marveled.

Back in 2002, she applied to the National Institute of Nursing Research for a grant to study non-healing wounds and was told her proposal was impossible to accomplish. That only motivated her to work harder and resubmit her proposal to obtain gene expression profiles from biopsies taken from the non-healing edge of patients’ venous ulcers. That work won NINR funding and has, to date, yielded a roster of some 1,557 genes that are de-regulated in non-healing wounds. It also established a new translational research field that has already changed clinical practice.

Tomic-Canic and her colleagues have employed what she calls “wound-omics” to distinguish tissue that is healing-competent from healing-incompetent.

The non-healing phenotype is characterized by loss of:

  • cellular migration
  • appropriate signals and response to growth factors, and
  • differentiation in the epidermis.

Further analysis, she said, identified two distinct cell/tissue phenotypes within chronic wounds—healing-impaired and healing-competent—that can be linked to clinical outcomes in patients.

Signal loss, she explained, originates from high protease activity, decrease of receptors and signaling molecules that mediate the signals, and an increase of specific miRNA molecules.

One approach to restore the healing phenotype is to use biomarker-guided removal of cells that are non-healing. “Gene profiles can serve as a guiding tool for surgical debridement—it’s, in a simplified sense, a kind of pregnancy test for wounds,” said Tomic-Canic. Her team’s goal is to uncover a small set of genes that will serve to predict what wound is healing, and to distinguish tissue within a wound that can heal from tissue that can’t.

“We are narrowing down the list of genes and cellular biomarkers,” she said. “Our hope is that one day there will be a gene chip for wounds.”

She thinks skin is the ideal tissue in which to attempt gene and progenitor cell therapy approaches, since it could be applied topically and temporarily, with a goal of restoring a healing phenotype. Cell sources could be from the patient’s own tissue; progenitor cells could be generated and introduced in a similar way.

“These are probably the most exciting times in biomedicine,” she enthused. “The good days are coming.” NIHRecord Icon


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