07 September 2018

Skin without a bioreactor

New skin was grown on an open wound

Ksenia Malysheva, Naked Science

A group of researchers from the Salk Institute for Biological Research in San Diego has developed a technique for converting cells on the surface of an open wound or ulcer into cells of the upper layer of the skin, the epithelium. In an article published in the journal Nature (Kurita et al., In vivo reprogramming of wound-resident cells generates skin epithelial tissue), scientists describe the process of returning cells on the wound surface to a state similar to that of a stem cell, and then directing them along the path of skin cell development. The technique is promising as a way to heal ulcers, burns, bedsores and skin damage in metabolic diseases such as diabetes. In addition, it can be used to counteract skin aging, the authors of the work believe.

The skin is capable of regeneration, but this ability weakens with age, so as the population ages, non-healing skin lesions become an increasingly common problem. Usually, skin grafting of the patient himself or skin grown in vitro from stem cells is used to accelerate healing. Juan Carlos Izpisua Belmonte and his colleagues managed to get the skin at the site of the injury without resorting to transplantation.

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Transformation of mesenchymal cells (red) into basal keratinocytes (green) on the surface of an extensive ulcer on the mouse skin. Figure from the press release of the Salk Institute The alchemy of healing: researchers turn open wounds into skin - VM.

The scientists worked with skin stem cells that differentiate by migrating from deep layers to the surface. Under normal conditions, these cells most often turn into keratinocytes, which make up 90% of healthy skin; however, when the integrity of the skin is violated, stem cells are mainly involved in the inflammatory process and do not form a new epithelium.

First, scientists isolated 55 proteins and RNA from the cells of the lower (basal) layer of the epidermis, which could potentially participate in the differentiation of stem cells along the path of keratinocytes. Then, by trial and error, four proteins were isolated, which most strongly influenced differentiation. After treating deep cuts on the skin of mice with a "cocktail" of these four proteins, scientists obtained a new epithelium on the surface of the cuts in 18 days. Three months and six months after the start of the experiment, cells from skin samples grown at the site of the cut turned out to be healthy according to a number of microbiological, genetic and other indicators.

Before starting clinical studies, scientists plan to test the technique on other models of skin lesions and make sure the method is safe.

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