Patchy Signal

A skin condition characterised by scaly red patches, psoriasis is an autoimmune disorder linked to dysfunctional immune signalling, causing inflammation and accelerating cell division in the outermost layer of skin, the epidermis. Treatments targeting a shared feature of signalling proteins interleukin-12 (IL-12) and interleukin-23 (IL-23) can alleviate symptoms, but later drugs affecting only IL-23 proved even more effective, prompting questions about the role of IL-12. By selectively deleting the receptor for IL-12 in epidermal skin cells, keratinocytes, in mice, researchers showed that IL-12 actually protects against psoriasis. In the skin samples above, dividing keratinocytes in the epidermis (left of the white line), are highlighted in red; cells possessing the IL-12 receptor (left panel) are dividing less than those lacking it (right), suggesting that IL-12 acts to reduce cell proliferation. Future therapies should therefore concentrate on IL-23, a result with potential implications for other conditions treated by blocking both proteins.

Written by Emmanuelle Briolat

Image from work by Pascale Zwicky and colleagues, University of Zurich

Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Image copyright held by the original authors

Research published in Science Immunology, October 2021

On the origins of acne Acne vulgaris is a chronic inflammatory skin condition that primarily affects adolescents and young adults. It has a prevalence of 80% in individuals aged between 11 and 30, therefore affecting approximately 9% of the world population. The complex etiology of acne involves genetic, hormonal and environmental factors. Acne presents with inflammatory and non-inflammatory…

High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes. – PubMed – NCBI

“Mitochondria are fascinating structures of the cellular compartments that generate energy to run the cells. However, inherent disorders of mitochondria due to diabetes can cause major disruption of metabolism that produces huge amount of reactive oxygen species (ROS). Here we study the elevated level of ROS provoked by high glucose (HG) environment triggered mitochondrial dysfunction,…

Bioprinting is rapidly becoming a hot trend in the world of medicine. Now a group of Spanish scientists has built a prototype 3D bio-printer that can create a fully functional human skin. The main idea is to build a machine, that can print custom body parts, to transplant them into a patient’s body. Printing custom tissues using a patient’s own body cells would help to eliminate the waiting time and the need for organ donors.

A bioprinter is essentially a 3D printer, but for the body. The printer takes help from the bio-inkin order to create askin. However, bio-ink is not the ink.Instead, it uses cellular components of skin, which include plasma, primary human fibroblast& keratinocytes.Bioink works the same way as the conventional printer ink, and in this case, the bio-links are mixed in such a way that it createsthe human skin. A computer controls the components of the printer that helps to print skin correctly. The printer can print up to 30 square inches of skin per hour, which is much faster than the present skin growing techniques.

The skin looks like a real human skin, which features an external layer for protection just like epidermis, and a thicker layer acts as the dermis. Additionally, it also contains a layer which is made up of fibroblast cells that help to produce a protein named collagen that provides the skin needed elasticity and strength.Read more..

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Generalised junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease, causing extreme fragility of the skin. Minor trauma can therefore elicit major blisters and skin erosion, ultimately resulting in the death of 40% of patients before they reach adolescence. 

In a previous clinical trial, local transplantation of transgenic epidermal cultures generated a functional layer of skin, with healing of the JEB skin lesions. However, only a very small area of skin was treated, calling for further investigation into a treatment for large skin lesions typical of generalised JED. In 2015, compassionate use of combined ex vivo cell and gene therapy was granted to treat a seven year old boy with severe JED. By the time of treatment, the patient had blisters all over his body and a shocking total epidermal loss of 80%.

A European group in Ruhr University, Germany, used a small biopsy taken from a non-blistered area of skin of the patient, isolated the keratinocytes, then cultured and transduced the cells using a retroviral vector expressing LAMB3 cDNA (the gene which was mutated in the patient). Over 6 months, epidermal grafts up to 0.85m2 in size were generated and transplanted onto the patient’s skin lesions in stages. The results published in a paper by Nature demonstrate that 1 month following transplantation, the grafts had completely integrated into the patient’s skin, and continued to spread to regenerate nearby areas of damaged epidermis. 

 A month following each transplantation, the grafts were demonstrated to have completely integrated into the skin, and continued to spread to regenerate nearby areas of missing epidermis. 80% of the patient’s epidermis had been regenerated using stem cell therapy, and 21 months following the procedure, the skin remained functional, sturdy and did not blister even when pinched. 

The fact that almost the entire epidermis of the patient was regenerated is an exciting and major breakthrough for cell and gene therapy, and demonstrates the potential of this treatment for generalised JED, in addition to other epidermolysis bullosa conditions.