Doctors fix genetic defect and grow boy new skin

09 November 2017
Posted by Chris Smith.

Doctors in Germany have used gene therapy to grow a complete new epidermis for a boy with a life-threatening inherited skin disease.

The boy was seven years old when he was admitted to hospital in 2015 with severe complications of junctional epidemolysis bullosa (JEB). This is a rare skin condition caused by faults in a handful of genes that code for anchor molecules that glue the surface skin layer, called the epidermis, to the deeper skin layer known as the dermis.

In affected patients the skin is extremely fragile to the extent that even very mild trauma or minor abrasions lead to severe and painful blistering, ulceration and scarring. The break-down in the skin also leaves patients susceptible to bacterial infections, and in the long term the chronic injury process, and relentless regenerative demands placed on the skin stem cells, mean that skin cancer is a common complication.

When the boy presented to hospital, an exacerbation in his disease meant that he'd already lost over half of the skin from his body, and he was suffering overwhelming infection with Staphylococcus aureus and Pseudomonas aeruginosa bacteria. 

Faced with these extreme injuries, and exceptional circumstances, doctors resorted to a highly experimental treatment - they used gene therapy to fix the genetic fault responsible for his disease in some stem cells, and then used tissue culture to grow the patient a replacement epidermis.

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Replacement skin grown from stem cells repaired by gene therapy

The new skin was prepared from a small patch of relatively intact epidermis recovered from the boy's groin area. Skin stem cells called keratinocytes were extracted from this 4cm2 piece of tissue and infected with a harmless virus reprogrammed to carry a healthy copy of the LAMB3 gene that was defective in the patient. The virus inserted the healthy LAMB3 gene into the DNA of the skin stem cells, restoring their ability to make healthy amounts of the protein Laminin-5, which gives skin its strength.

The corrected cells were grown in culture, either on a plastic scaffolding or on a matrix of a molecule called fibrin which the body naturally uses to make blood clots and provides a strong foundation for tissue to grow.

Over about 12 weeks, the German team were able to grow nearly a square metre of new skin from the genetically repaired stem cells. Sheets of this new epidermis were transplanted onto the patient, replacing his damaged tissue and meshing together like a patchwork. By the end of his treatment, nearly all of the patient's body was covered with the treated skin.

Now, two years later, the patient is well and back at school. His skin is robust and resilient, he does not need to use any medication, and if he cuts himself his skin heals normally.

The team, who have published their remarkable work in the journal Nature this week, will continue to monitor him closely though, because there is a chance that genetic changes introduced into the repaired stem cells during the procedure could lead to malignancy. That said, tests done at the time of transplant and subsequently, have not shown any evidence of untoward genetic alterations.

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