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U-M team treating mouth wounds by engineering tissue grafts


University of Michigan researchers are testing a new procedure in which they can take a tiny piece of a person’s mouth lining, grow it into a dollar-bill sized piece of tissue and graft that expanded piece into the donor’s mouth to heal a wound.

Dr. Stephen Feinberg is leading a team that is currently working with five patients to treat small mouth wounds with the grafts. These five patients are part of what is called a proof of concept study for the Food and Drug Administration.

Feinberg, a professor of both dentistry and surgery, is collaborating with Kenji Izumi, a scientist and surgeon who already has seen success with the method in about 80 patients in Japan. Izumi is a visiting assistant research scientist at U-M and a long-time colleague of Feinberg’s.

Many types of people have trouble with mouth wounds that do not heal well on their own---patients going through cancer chemotherapy, for example, or people with diabetes. Those who have been involved in accidents are candidates, as well.

Existing treatments include taking a skin graft from a site such as a leg and stitching it into the mouth. Skin works for covering the wound, but is not as pliable as the mucosal lining of the mouth, and if it is too thick, it might even grow hair inside the mouth. A large skin graft also leaves the patient in pain with lengthy healing time.

Feinberg said tissue engineering has many advantages, including a smaller donor site that heals faster and a graft that is mucosal cells, more like the mouth lining, not skin. After a short healing period, the patient feels mouth lining as it is supposed to feel.

In their research, Feinberg and Izumi took thin pieces of mucosa from the roof of the patients’ mouths, about as big around as the end of a pencil eraser. They worked with Cynthia Marcelo, a research professor of surgery with nearly a decade of expertise in cell growth, to use a system she developed that encourages the cells to reproduce more rapidly in a well-defined system acceptable to the FDA. This special environment helps a tiny piece of mucosal mouth lining grow to the size of a quarter within a few weeks, and a dollar bill within about a month.

The team attaches the expanded cells to a piece of AlloDerm, a specially prepared piece of human dermis made by LifeCell Corp. The composite of cells and AlloDerm is then immersed in a Petri dish with a liquid Izumi casually compares to plant food. The liquid contains proteins and vitamins, the nutrients that encourage the cells to grow faster and increase in numbers.

Feinberg and Isumi use the U-M Human Application Lab in University Hospital, an ultra-clean facility that follows the FDA’s strict regulations for keeping out potential contaminants. Everyone who enters must wear elaborate protective gear, and before Izumi works with growing tissue samples, he must sterilize the work area and his gloves. Every precaution protects the tissue cultures from exposure to dirt, skin cells or anything else that might cause a problem once the cells are implanted in a human.

The team is working with five patients to demonstrate proof of concept. That is the precursor to moving into the trials that inform an FDA decision to approve a new medical treatment. Following successful completion of the preliminary studies, Feinberg plans to seek FDA approval for a larger clinical trial involving 50 patients.

Feinberg is working with U-M Technology Transfer to identify companies that might have an interest in commercializing the treatment so it can be easily put into practice by others. Eventually, Feinberg hopes to see the treatment used not only for small mouth wounds but for major reconstructive surgery where the patient cannot physically donate enough tissue for repairs.

Though this treatment is still in the early stages of approval, Feinberg already is looking down the road. He has begun to separate the stem cells from the harvested piece of tissue, because stem cells divide more rapidly and can live longer, aiming to eventually produce grafts solely from stem cells. He is also interested in modifying the approach to infuse the piece of tissue with gene therapy compounds, meaning the implanted tissue might help a person with such chronic conditions as diabetes or systemic illnesses like diabetes or hemophilia.

Feinberg and his team are among dozens of researchers at U-M working on tissue engineering techniques and applications. Some aim to generate tooth or bone to aid in healing, others focus on softer tissues like skin, but all are looking at the next generation treatment that involves having a patient’s own body provide the building blocks for healing itself. This research is supported by a $1.25 million grant from the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health.

Colleen Newvine | EurekAlert!
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