Human stem cells repair radiation-damaged skin

Scottsdale, Ariz. - A recent trial involving 20 patients with radiation side effects provides some of the first clinical proof that stem cells are capable of repairing damaged human skin.

"This is one of the first real clinical works demonstrating effectiveness of stem cells in a clinical setting," says Gino Rigotti, M.D., who heads the plastic surgery department at the Azienda Ospedaliera Verona, Italy.

Most previous stem cell research involves animal models, while a few isolated case reports involving human patients do exist.

Trial specifics

In the trial, researchers treated consenting patients suffering from side effects of radiation treatment recognized as a previously undescribed scleroderma-like microangiopathy. They gave each patient injections of adult mesenchymal stem cells (AMSCs) together with the cells' natural three-dimensional scaffold, applied directly to the radio-damaged areas in accordance with optimal patterns determined by a computer-based procedure.

"We determined that the radio-damaged tissue was a scleroderma-like ischemic lesion because of factors including the space between adipocytes, the edema and the fibrosis. We demonstrated with our research that therapy with adipose-derived stem cells is effective for the care of this lesion," Dr. Rigotti explains.

In particular, he says all aspects of the lesions were approaching normalcy after treatment, as measured by ultrastructural studies performed on tissue samples from the radio-damaged areas before transplantation and after periods ranging from one to 12 months post-therapy. Researchers also performed ultrastructural studies on the lipoaspirate, as well as cytofluorimetric examination.

Cytofluorimetric examination of human lipoaspirate (which researchers harvested with a number 2 cannula) revealed that after purification and centrifugation, this material contained at least 1.8x10³ AMSCs/cc. Therefore, researchers deemed cell culturing unnecessary.

"Stem cells were not placed in culture for three reasons," Dr. Rigotti says. "First, previous research on animals has demonstrated that stem cells are more effective if they are (preserved) in a three-dimensional structure. Second, placing any kind of cells in culture creates a risk of microorganism contamination. Third, the cost of cell culturing can be prohibitive."

Clinical results

As for clinical results achieved by the uncultured stem cells, ultrastructural analysis showed that newly formed microcirculation addressed radiation-induced alterations in microcirculation. In keeping with these findings, a group of 11 patients with LENT SOMA grade four damage progressed to grade zero over the course of the trial. Five patients with grade four damage achieved grade one, while two reached grade two. Among nine patients who began with grade three damage, five progressed to zero; four progressed to grade one.

Dr. Rigotti says, "We saw that adipocytes were preserved and that there was no fibrosis between the adipocytes. Capillaries also lost every aspect of radio-damage. In summary, it is quite normal tissue. And most importantly, we were able to document an increasing number of capillary vessels. That means that the stem cells are provoking angiogenesis."

Human adipose mesenchymal stem cells recently have been found to secrete angiogenic factors in mice (Rehman J et al. Circulation. (2004) 109(10):1292-1298.). However, prior to Dr. Rigotti's research they had not been used for ischemic tissue neovascularization in humans.

Other implications

Dr. Rigotti says his study demonstrates the therapeutic efficacy of AMSCs for treating radiation damage through a process that replaces damaged tissue with reconstructed normal tissue. Additional benefits of his method include the fact that its AMSC procurement method is easy and safe for patients.

As a consequence of his findings, he adds, "Probably all ischemic lesions, including lesions due to arteriosclerosis and diabetes, can be improved through stem cell therapy."