Transplants Using Patients’ Own Skin May Be Safe, Effective Treatment for RDEB, Trial Suggests

Transplanting a patient’s own healthy skin to treat their skin ulcers was found to be safe and effective for three people with recessive dystrophic epidermolysis bullosa (RDEB) for more than one year, a clinical trial shows.

The study, “Cultured epidermal autografts from clinically revertant skin as a potential wound treatment for recessive dystrophic epidermolysis bullosa,” was published in the Journal of Investigative Dermatology.

Developing regenerative treatments for epidermolysis bullosa (EB) has been challenging, researchers say, due to the elimination of transplanted cells by the host’s immune system. Clinicians also face limitations in using a patient’s own cells, unless the individual’s genetic defects have been corrected.

Cultured epidermal autografts (CEAs) — a technique that provides a permanent skin replacement using the patient’s own tissue — have been used in people with severe burns with proven long-term safety.

Cases of adults with EB with areas of normal-looking skin and no blister formation have been shown in substantial studies. In these people, a portion of the keratinocytes — the main cell type in the skin’s outer layer, the epidermis — correct the causative gene mutations, which is called revertant mosaicism (RM).

In a prior study, a team from Japan described a 12-year-old boy with RDEB who received CEA treatment in 2001 for a refractory ulcer on the right knee. The CEAs, collected from his back, eased the ulcer within one month. After 16 years, the treated knee remained in good condition, with no blisters or erosions.

Imaging analysis of the knee showed greater build-up of type VII collagen (COL7) — a key protein to keep the dermal and epidermal skin layers attached. It also showed more and thicker anchoring fibrils, which are large structures mainly composed of COL7. Then, analysis of the COL7A1 gene suggested the occurrence of RM in the treated skin.

Subsequent observations in five adults with RDEB further showed areas of revertant skin. Based on those observations, the scientists hypothesized that RM may be frequent in RDEB patients treated with CEA.

To test this hypothesis, the team conducted a single-center, Phase 2 clinical trial with three patients recruited at Hokkaido University Hospital. The three had eight ulcers suitable for CEA.

After the observation period, one of the participants — patient 2 — experienced squamous cell carcinoma twice on the knees and the left hand, which was unrelated to the CEA transplant sites or skin harvest areas.

All treated ulcers showed epithelization — formation of new skin tissue — within two weeks after CEA treatment. Patient 1 showed increasing epithelization toward 100% at week 24. Patient 2 showed full tissue formation as early as week 4, with the skin remaining in excellent condition for more than 52 weeks.

Patient 3 required four transplants due to four re-ulcerations, showing a gradual decrease in epithelization from week 24.

Taken together, the mean epithelization rate across the three patients four weeks after the last CEA transplant was 81.6%. That achieved the trial’s primary goal of having a rate higher than 50%, and not being inferior to that of treated burns, the researchers said.

The investigators subsequently assessed whether RM occurred in patient 1 at week 24. No significant changes in COL7 levels were seen in the grafted skin, although there was an increase in anchoring fibrils. Then, genetic analysis in the same patient revealed RM in both donor and treated skin areas, which was key for the long-term epithelization of the ulcers.

“In conclusion, CEAs from clinically normal skin have the potential to be a safe, simple, long-term local treatment option for severe RDEB,” the scientists said.