New skin

German doctors have grown transgenic skin for 80% of the baby's body

Anatoly Alizar, Geektimes

Left: demonstration of normal functionality and elasticity of transgenic skin. On the right: no formation of blisters in the places where the biopsy was taken after transplantation.
Photo from the article by Hirsch et al.
Regeneration of the entire human epidermis using transgenic stem cells, published in Nature.

In June 2015, a seven-year-old boy was admitted to the burn department of a German hospital, the entire surface of whose skin was covered with blisters. Their cause was not burns, but a rare genetic disease called epidermolysis bullosa (epidermolysis bullosa). Because of him, the child lost 80% of the outer layer of the epidermis, opening the way to life-threatening infections. 

The cause of this genetic disease is a mutation in the genes encoding laminin-332 – a key component of the basement membranes, a thin cell-free layer separating connective tissue from the epithelium. Patients with this diagnosis often die at an early age, and survivors develop chronic damage to the skin and mucous membrane, which complicates life (such children literally cannot be touched) and leads to skin cancer.

Given the threat to the child's life, he was considered a suitable patient to test the regeneration of an almost complete epidermis from transgenic stem cells. An international group of European scientists and doctors have grown and transplanted a new skin to the boy, which covers 80% of the body, including almost entirely the arms, legs and back.

Scientists have experimented with this method of gene therapy before, growing small fragments of skin from the patient's stem cells. For example, a group from Stanford University (USA) is working on the same project together with the biotechnology company Abeona, but they say they have never thought about a complete transplant of the patient's skin, and grow only small sheets for damaged areas. This operation in Germany represents the world's largest demonstration of transgenic skin.

There are three main types of epidermolysis bullosa. In this case, the boy's cells contained mutated copies of the LAMB3 gene, which, as already mentioned, encodes laminin-332 and helps strengthen the epidermis. 

The researchers extracted cells from intact areas of the skin. Stem cells capable of recreating new skin were isolated from these samples (as is known, a person is constantly undergoing the process of regeneration of the epidermis). As part of the transgenic operation, stem cells were infected with a specially designed virus that is programmed to change mutated copies of the LAMB3 gene to normal copies. After a kind of "genetic recoding", scientists began to grow sheets of healthy stem cells on a plastic base, which were then implanted on the patient's skin.

A sheet of transgenic stem cells. Photo: Center for Regenerative Medicine, University of Modena and Reggio Emilia (Italy).

The grown leaves had different sizes: from 5 ×7 cm to 13 ×13 cm. 

Skin transplantation on 80% of the body surface required three operations. More than 21 months have passed since then. The regeneration of the skin in the reconstructed areas is carried out normally, without the formation of blisters. The child was finally able to return to school and even plays football, scientists report. They believe that there will no longer be a need to perform repeated operations to implant new sheets of stem cells. Apparently, the genetic disease has been completely cured – most of the wrong copies of the gene have been replaced with the correct version. The new skin will stay with the person forever and will constantly regenerate with the already correct LAMB3 gene.

According to experts, gene therapy is the best treatment option for patients with epidermolysis bullosa, since there are no drugs for this disease. (In mice, this has already been done without skin grafting, using gene editing directly in diseased cells – VM.) Around the world, about 500,000 people suffer from this type of mutation. For them, the opportunity to get real healthy transgenic skin means the beginning of a new, fulfilling life.

Below are two more pictures from the article in Nature, but it's better not to look at them for the faint of heart – VM.

A patient with the loss of 80% of the outer layer of the epidermis.

Regeneration of the skin with the help of transgenic cultures. Implantation of plastic sheets with genetically modified stem cells on the left arm and back is shown, the healing process after one month (f, h) and after four months (i).

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