Media ReleaseFrom: Springer Nature
Medical research: Reconstructing the skin
Embargo —Sydney: Thursday 09 November 2017 05:00 (AEDT)
A fully functional epidermis, covering approximately 80% of the total body surface area, has been reconstructed for a seven-year-old patient with a genetic skin disease called Junctional Epidermolysis Bullosa (JEB). The findings are reported in Nature this week.
JEB is a severe, often lethal, genetic disease that causes the skin to become fragile. Mutations in the genes LAMA3, LAMB3 or LAMC2 affect a protein called laminin-332 — a component of the basement membrane of the epidermis — leading to blistering of the skin and chronic wounds, which impair the patient’s quality of life and can lead to skin cancer.
Previously, the treatment of two patients has provided evidence that transplantation of transgenic epidermal cultures — groups of genetically modified epidermal cells — can generate a functional epidermis leading to correction of JEB skin lesions. However, only a small area of skin was reconstructed.
Using skin cells taken from a non-blistering area of the seven-year-old patient’s body, Michele De Luca and colleagues were able to reconstruct the epidermis. From the skin cells, the authors established primary keratinocyte cultures, which were genetically modified using a retroviral vector to contain the non-mutated form of the gene LAMB3. Sequential transgenic epidermal grafts were applied on a properly prepared dermal wound bed, so as to cover the patient’s affected body surface.
Over the course of the next 21 months, the regenerated epidermis firmly adhered to the underlying dermis, even after induced mechanical stress, healed normally, and did not form blisters.
Through the process of clonal tracing, the authors found that the human epidermis is sustained by a limited number of long-lived stem cells which are able to extensively self-renew and can produce progenitors that replenish terminally differentiated keratinocytes.