Stem cell technology: Novel treatment shows promise for nonhealing digital ulcers

September 1, 2009

A combination therapy using stem cells and bioengineered skin has proven to be very effective in closing the digital ulcers occurring in scleroderma patients.

Key Points

Boston - Stem cells have been used for the treatment of difficult-to-heal cutaneous wounds, such as diabetic and venous leg ulcers, as well as large defects following skin cancer surgery. Recent research has shown that this therapeutic approach not only can help close other cutaneous wounds, but it can do so quickly, bringing much-needed relief to these patients.

"After achieving very positive results in leg ulcers by using stem cell technology, we applied this approach with the addition of bioengineered skin to the digital ulcers seen in systemic sclerosis (scleroderma) patients and managed to close the wounds within two weeks.

"For cutaneous wounds that are difficult to heal, the use of stem cells combined with bioengineered skin appears to be a promising therapeutic option, as wounds' closure speed is dramatic," says Vincent Falanga, M.D., F.A.C.P., professor of dermatology and biochemistry at Boston University, Boston, and chairman of the department of dermatology and skin surgery at Roger Williams Medical Center in Providence, R.I. He is also the principal investigator of a recently renewed National Institutes of Health Center of Biomedical Research Excellence at the medical center, totally focused on tissue repair and stem cells.

"Mesenchymal stem cells can further differentiate into other cell types, and we believe that the combination of these cell cultures with bioengineered skin gives these multipotent cells the right direction that can help in stimulating the healing process in cutaneous wounds recalcitrant to standard therapies," Dr. Falanga says.

Fingertip ulcers

Using stem cell technology, Dr. Falanga and colleagues conducted a study in an attempt to heal the painful finger-tip ulcers which commonly occur in patients with scleroderma.

In the three-patient trial, a bone marrow aspirate was taken from each patient. From this sample, mesenchymal stem cells were then grown in culture. Using a specially designed fibrin spray delivery system which consists of a mixture of fibrin and the grown mesenchymal cell cultures, Dr. Falanga performed two spray treatments on the digital wounds of the patients and additionally covered the wound with bioengineered skin.

The bi-layered substitute skin, consisting of keratinocytes and fibroblasts, was derived from neonatal foreskin and served as a biological unit and stimulus for the mesenchymal stem cells to differentiate and reconstitute the wound bed.

Results showed that the cutaneous ulcerations closed very quickly, within two weeks of therapy. The fingertips of scleroderma patients often have a sunken-in appearance and scars, likely due to the poor blood supply to the area. The novel spray therapy not only resulted in a quick healing of the ulcers but also a leveling off of the skin depressions, which is most likely due to formation of new dermis.

"The novel fibrin spray delivery system works by mixing highly diluted fibrinogen and thrombin together with mesenchymal stem cells in a single syringe system. This system allows for immediate polymerization or gluing of the stem cells to the surface of the wound, making the treatment easy, clean and quick," Dr. Falanga says.

'Didactic' instruction

Dr. Falanga emphasizes the need for stem cells to be used responsibly and to be introduced in the right environment. His hypothesis and the present results suggest that stem cells will need what he calls "didactic" components to give instruction or messages to the stem cells to develop into a given tissue.

"Adult stem cells can be used for many different applications, particularly in repair processes, and I believe that cutaneous wounds are a good and safe model for testing many of the potential systemic applications of stem cells in general," Dr. Falanga says.

Disclosure: Dr. Falanga has conducted research for Organogenesis, Canton, Mass.