Autologous-cultured fibroblasts fix dermal defects

Key Points

Baltimore - Fibroblasts cultured from patients' own tissues appear to provide long-lasting correction of rhytids, acne scars and other facial contour deformities, according to a recent study.

In the 158-patient randomized study, "Autologous fibroblasts, when reinjected, seemed to remodel scars automatically and improved superficial wrinkles to an impressive extent" (Weiss RA et al. Dermatol Surg. 2007;33:263-268), says Robert A. Weiss, M.D., associate professor, department of dermatology, Johns Hopkins University School of Medicine, and lead researcher.

Researchers first randomized patients in a double-blinded 3:1 fashion to receive either live fibroblast cells or placebo injections. Then, they took postauricular skin biopsies and sent them to a laboratory (Isolagen Technologies, Exton, Pa.) for selection, culturing and multiplying, using a proprietary process that yielded approximately 20 million cells per ml.

For anesthesia, they used only cold application - no injected or topical anesthetics, Dr. Weiss tells Dermatology Times.

In total, investigators treated 215 facial contour defects.

Researchers evaluated results one, two, four, six, nine and 12 months after patients' initial injections.

Though they used no patient photos for grading purposes, beginning four months after the start of treatment, investigators made live evaluations of patients against a standardized seven-point photo guide, Dr. Weiss says.

Rather than using existing photographic scales, Dr. Weiss says by enhancing standard images with Photoshop (Adobe) so each could be seen from a consistent angle, "We came up with a scale that we thought accurately reflected both depth of scarring and of nasolabial fine lines." Overall, investigators sought a two-point shift in at least one treated area to consider patients responders.

During the study, researchers excluded six patients for reasons such as voluntary withdrawal, investigator withdrawal or having received additional cosmetic treatments. Of 145 evaluable patients left, 106 received live fibroblast injections; 39 got placebo injections.

Throughout the study, Dr. Weiss says, "The proportion of responders was dramatically higher in the Isolagen-treated group," with the disparity achieving statistical significance (p<.0001) at six months. At one month, for example, response rates were 54.4 percent among treated patients, 30.8 percent among placebo recipients.

At two months, he says treated patients' response rate increased to more than 73 percent, while the placebo responder rate remained relatively flat at all evaluation intervals.

Nine and 12 months after the first injection, fibroblast-treated patients continued to show benefits, with response rates of 75 and 81.6 percent, respectively, Dr. Weiss says.

Patients treated for acne scars achieved particularly pronounced results, with a six-month response rate of 48.4 percent, versus 7.7 percent for placebo, Dr. Weiss notes. For nasolabial folds, the response rate at six months was 42.2 percent among treated patients versus 10 percent for placebo.

"There seemed to be a very low risk of side effects. We didn't see any, other than a little redness for a few hours postinjection," says Dr. Weiss.

Though the treatment remains experimental, Dr. Weiss adds, "We're hoping it will be cleared by the Food and Drug Administration in early 2008." At press time, the treatment was undergoing pivotal phase 3 clinical trials for wrinkles/nasolabial folds, according to a May 10 Isolagen quarterly report.

Although the culturing process took approximately six weeks at the time of the study, Dr. Weiss says the manufacturer has since improved its culturing technique to produce more fibroblasts in just four weeks.

"We've followed some of these patients now for more than two years," he says.

In patients with acne scars whom he has seen after the study for other reasons, Dr. Weiss says, "Results have certainly been very long-lasting."

Disclosure: Isolagen funded the study and paid Dr. Weiss as a consultant in the past, though he owns no company stock and has no present affiliation.

For more information: http://www.aad.org/