Scientists at the University of Modena and Reggio Emilia have evaluated a patient with a genetic skin disorder known as epidermolysis bullosa (EB) almost seven years after he had undergone a gene therapy procedure as part of a clinical trial. The study revealed that a small number of skin stem cells transplanted into the patient’s legs were sufficient to restore normal skin function, without causing any adverse side effects.

“These findings pave the way for the future safe use of epidermal stem cells for combined cell and gene therapy of epidermolysis bullosa and other genetic skin diseases,” said the University of Modena and Reggio Emilia’s Michele De Luca, M.D., senior author of the study (“Long-Term Stability and Safety of Transgenic Cultured Epidermal Stem Cells in Gene Therapy of Junctional Epidermolysis Bullosa”), which appears in Stem Cell Reports.

EB is a painful condition that causes the skin to be fragile and to blister easily. It can also cause life-threatening infections. Because there is no cure for the disease, current treatment strategies focus on relieving symptoms.

To evaluate stem cell-based gene therapy as a potential treatment, Dr. De Luca and his colleagues previously launched a Phase I/II clinical trial at the University of Modena and recruited an EB patient named Claudio. The researchers took skin stem cells from Claudio’s palm, corrected the genetic defect in these cells, and then transplanted them into Claudio’s upper legs.

In the new study, Dr. De Luca and his team found that this treatment resulted in long-term restoration of normal skin function. Nearly seven years later, Claudio’s upper legs looked normal and did not show signs of blisters, and there was no evidence of tumor development. Remarkably, a small number of transplanted stem cells was sufficient for long-lasting skin regeneration.

“These data demonstrate that the regenerated transgenic epidermis is fully functional and virtually indistinguishable from a normal epidermis, the vast majority of transduced keratinocytes are transit-amplifying progenitors that are lost within a few months after grafting, and the regenerated epidermis is sustained by a discrete number of engrafted, long-lasting, self-renewing transgenic stem cells,” wrote the investigators.

Even though Claudio’s skin had undergone about 80 cycles of renewal during this time period, the transplanted stem cells still retained molecular features of palm skin cells and did not adopt features of leg skin cells.

“This finding suggests that adult stem cells primarily regenerate the tissue in which they normally reside, with little plasticity to regenerate other tissues,” noted Dr. De Luca says. “This calls into question the supposed plasticity of adult stem cells and highlights the need to carefully chose the right type of stem cell for therapeutic tissue regeneration.”

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