Seven Year Old Gets New Skin: Avenues in ‘Stem Cell Based Gene Therapies’

A stem cell based transgenic skin. Image credits: Frank Jacobsen
HUMAN SKIN

The largest organ in the human body, the skin is often overlooked in comparison to other “important organs”. This could be due to its “guarding” function or could be due to its non-critical life support.

Generally, human skin constitutes several layers but majorly two; Epidermis and Dermis. These layers are attached together by a special class of proteins called Laminin 332.

Any mutation in the Laminin 332 synthesizing genes leads to the failure in the attachment of these two layers making skin loose and prone to rupture at slight injury, friction, and scratches.

Structure of human skin
Structure of human skin. Image credits: humananatomyly.com

Junctional epidermolysis bullosa (JEB) is a rare genetic and inherited disease. It is caused by a mutation in laminin 332 gene which causes upper epidermis to separate from the lower dermis. This leads to blisters and chronic wounds on the skin of the patient.

Although the frequency of this genetic defect is less than 1 million people, it is rapidly rising.

CASE STUDY

One such case was of a seven-year-old child suffering from a life-threatening form of JEB. He was admitted to the Burn Unit of the Children’s Hospital at the University in January 2015. At that time, his body lost about 80% of normal epidermis. This is when a team of doctors and researchers at the Ruhr-University decided to use combined ex vivo cell and gene therapy to regenerate the full epidermis of the child.

The study published in Nature, regenerated the entire epidermis of the child by using transgenic stem cells. Normal (non-blistering) keratinocytes, the epithelial cells taken from the biopsy of abdomen region of the patient were cultured to synthesize a healthy Laminin 332 gene by means of retroviral-mediated gene transfers.

These transgenic epidermal grafts were then used to restore about 80% of patient’s total body surface.

Artificial human skin regeneration.
Regeneration of artificial human skin. Image credits: Nature

Transplanting 80 percent of the skin and providing intensive medical care to the patient over a period of eight months was extremely challenging,” says Tobias Hirsch, lead author of the study.

TRANSGENIC SKIN

Punch biopsies taken randomly at 4, 8 and 21 months after grafting showed that the epidermis had normal morphology and had no blisters, erosions or epidermal detachment from the underlying dermis.

In situ hybridization, a technique used to reveal the location of specific DNA/RNA sequences on chromosomes or in tissues showed that the regenerated epidermis consisted only of transgenic keratinocytes.It also showed that the transgenic epidermis expressed virtually identical amounts of laminin 332-β 3, which was located at the epidermis-dermis junction.

The patient was discharged in February 2016. His epidermis is currently stable and robust and does not blister, itch, or require ointment or medications.

This approach has enormous potential for research into and development of new therapies for the treatment of epidermolysis bullosa as well as other diseases and trauma causing large skin defects,” says Tobias Hirsch.

This could be a boon for people with life-threatening burns. Science is really making our lives better.

Source Ruhr-University Nature

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