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Rare Skin Disorder and Damaged Eyes Treated with Related Stem Cell Methods

European Science Foundation, October 23, 2007

Sufferers of a rare and debilitating skin disease may be aided by a combination of gene therapy and stem cells according to scientists and doctors in Italy. The same team also showed how stem cells can repair damaged eyes.

To generate new organs or tissues, stem cells, which are essentially ‘blank’ cells (‘toti- or ‘pluripotent’) that have not differentiated into specialized cells, are used in therapy. Stem cells have already been used for a number of years to treat burns said Professor Michele De Luca of the University of Modena and Reggio Emilia*. However, aside from this fact and other emerging treatments, he says that we still need to wait several years before stem cells therapy is widespread. The body's own population of stem cells continually regenerates many tissues. For decades, doctors have treated burn patients by culturing cells into new skin that can be grafted onto the wound. This was done by using small samples of skin specific stem cells called holoclones.

New cells deriving from an area surrounding the cornea called the limbus ,constantly replace the cells of the transparent outer covering of the eye called the cornea according to Professor De Luca’s team's research. These cells migrate to the cornea after differentiating into corneal epithelium.

“If the cornea is damaged severely by a chemical burn or infection, for example, it can become opaque and necessitates a transplant,” Professor De Luca told the meeting. “However, a transplant will only be successful if the patient’s limbus has remained intact so that it can continue to replenish the new cornea.”

Because they did not appreciate the requirement for the limbus, the reason why transplants failed escaped doctors for many years.

Professor De Luca's team decided to grow a new cornea from limbal stem cells taken from the healthy eye in order to treat patients who had a very small chance of ever regaining their sight. These patients, with eyes consisting of a destroyed limbus, benefited from the existing science behind using stem cells for treating burns.

It was possible to culture a new cornea and graft it on to the damaged eye by removing a small sample of these cells. The cornea regenerated successfully in 70% of cases, in 240 patients who were operated on with this procedure.

Due to faulty proteins that effectively anchor the surface layers of skin to the body, the skin becomes highly fragile and prone to blistering in a syndrome called Epidermolysis Bullosa. This rare but debilitating genetic disease of the skin now commands the attention of the researchers.

One of the anchoring proteins called laminin 5 develops a mutation in one form of the disease. On one patient, a 37-year-old male, a small scale trial of a novel gene therapy was conducted by Italian researchers on a small part of his body after consent was obtained.

“Because the patient’s body was so badly affected it was difficult to isolate any stem cells from his skin,” Professor De Luca told the conference.

“Most people have between seven and ten per cent of holoclones. Our man had none. Eventually we found a few in the palms of his hand and cultured them from a biopsy.”

The team grafted the new tissue onto the patient’s body after using gene therapy to insert the correct laminin gene into the growing cells.

Without flaking or blistering, the skin remained normal after several months indicating a successful graft.

This demonstrates that it is possible to use stem cells in gene therapy for genetic skin disorders,” Professor De Luca said.

*In conjunction with the National Research Council of Italy, the European Science Foundation’s EuroSTELLS stem cell program organized an international meeting of stem cell scientists in Milan (30 Sep – 2 Oct, “Challenges in Stem Cell Differentiation and Transplantation”) where Professor Michele De Luca described the work.


 

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