AAD 2009: Stem-Cell Therapy May Resolve Ulcers Associated With Scleroderma

Bob Roehr

March 11, 2009

March 11, 2009 (San Francisco, California) — Stem cells are at the center of a new therapeutic approach to treating skin manifestations of scleroderma. Preliminary results from 3 patients were presented here at the American Academy of Dermatology 67th Annual Meeting. The procedure was also used with success in 9 patients with nonhealing wounds without scleroderma.

The process uses autologous bone-marrow-derived stem cells, which are mesenchymal stem cells that can differentiate into the full range of skin and muscle cell types. Principal researcher Vincent Falanga, MD, described the research that is taking place at the Roger Williams Medical Center, in Providence, Rhode Island.

The cells are cultured ex vivo and their numbers are expanded greatly. A solution of the stem cells and fibrinogen is placed in 1 chamber of a double-chambered syringe, and the second chamber is filled with a solution of dilute thrombin.

The 2 solutions combine when ejected from the syringe as a spray over the wound. The mix begins to polymerize, and that "clotting" helps to hold the stem cells in place in the wound. The wound is then covered with 2-layer bioengineered skin, containing a layer of keratinocytes and a layer of fibroblasts.

Dr. Falanga said he believes the skin helps to create a "didactic" environment in which the constellation of cellular signaling molecules helps direct the stem cells to fill the gaps, restoring the entire tissue compartment.

But stem cells alone are not enough, Dr. Falanga said. They need to be coaxed into conduct appropriate to their context. That may include removing dead tissue, preparing or conditioning the site foundation, and providing a roof or cap to create a milieu in which the stem cells can thrive. Optimizing this environment will be a principal line of ongoing research.

"Pain relief was very rapid" for patients receiving the procedure, said Dr. Falanga. He showed slides of substantial healing at 4 and 8 weeks, noting that "this patient had not been free of ulcers for 8 years."

This proof-of-concept procedure has been applied to 9 patients with nonhealing ulcers without scleroderma and to 3 patients with nonhealing wounds related to scleroderma. After 6 months of follow-up, 4 patients healed completely and the others improved significantly, "with improved quality of life."

Treatment was limited by the study protocol to 3 cycles of stem cells. Dr. Falanga anticipates that some patients might benefit from additional cycles. The US Food and Drug Administration is reviewing plans to expand on this initial work, he said.

The process is unusual in that it also results in the creation of elastic fibers, which typically are not produced through normal wound healing, Dr. Falanga noted. This suggests that tissue generated through this use of stem cells differs in some substantive ways from normal healing.

The researchers found a dose response. "A major contribution of our research is that you can't just take a few cells and put them in a wound to achieve these results. We calculated that you need at least 1.5 to 2 million cells/cm2 for the wound to decrease in size," he said.

Dr. Falanga has also applied the process to large wounds resulting from the excision of cancers. "It has led to a good result with very little contraction" or scarring — yet another difference from normal wound healing.

He made the case that the skin is the logical place to test principles of stem-cell science because it is open to observation and intervention, whereas internal organs are not. That makes it much easier to manipulate and maximize the environment surrounding the stem cells.

Dr. Falanga told Medscape Dermatology that he was encouraged by the news that President Obama is lifting the ban on federal funding for embryonic stem-cell research. Even though his current work does not involve embryonic cells, he said, "you need the embryonic as a control."

Ali Hendi, MD, a Mohs and dermatology surgeon in Bethesda, Maryland, is excited by the findings. He called nonhealing wounds "a particularly challenging problem in medicine. Even with the best care, certain wounds, such as those in patients with scleroderma, do not heal." That increases the risk for soft tissue and bone infection with possible serious outcomes.

Dr. Hendi called the new approach "almost futuristic . . .to be able to spray stem cells on a chronically open wound and have it heal up. [This is] modern medicine at its best!" But Dr. Hendi did point out that these findings need to be confirmed in larger and controlled studies.

The research was funded by the National Institutes of Health. Dr. Falanga and Dr. Hendi have disclosed no relevant financial relationships.

American Academy of Dermatology (AAD) 67th Annual Meeting: Forum F110. Presented March 10, 2009.