New technique heals wounds with reprogrammed skin cells

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Juan Carlos Izpisua Belmonte, University of California, San Diego

(CONVERSATION) People with severe burns, pressure ulcers or chronic diseases such as diabetes may develop wounds called skin ulcers, which can spread through many layers of the skin.

In addition to being extremely painful, these sores can lead to serious or sometimes fatal infections or amputations. Generally, these ulcers are treated by surgical transplantation of the existing skin to cover the wound. However, when the ulcer is particularly large, it can be difficult to graft enough skin. In such cases, researchers can isolate stem cells from a patient's skin, cultivate them in the laboratory and transplant them into the patient. But the procedure is long, risky for the patient and not necessarily effective.

The dramatic rise in diabetes rates alone underlines the urgent need to develop new and effective methods for the treatment of skin ulcers.

My laboratory at the Salk Institute focuses on developing stem cell-based approaches to "reprogram" cells from one type to another for regenerative medicine.

In a report published in the journal Nature, we describe a new technique for directly converting cells naturally present in an open wound into new skin cells by reprogramming injured cells into a stem-cell-like state, in which the cells return to normal. older. more flexible state from which they can develop into different types of cells.

Masakazu Kurita, a postdoctoral research associate in my lab, who has a background in plastic surgery, knew that a critical step in healing was the migration of stem cells called basal keratinocytes – from near and intact skin – into wounds.

Basal keratinocytes are precursors of many types of skin cells. But large major wounds such as skin ulcers no longer present basal keratinocytes. In addition, as these wounds heal, the cells that multiply in the area – called mesenchymal cells – intervene primarily in wound closure and inflammation, but they can not rebuild healthy skin.

We wanted to convert these mesenchymal cells into basal keratinocytes, without ever taking them out of the body.

To do this, we compared the levels of different proteins inside the two cell types – mesenchymal cells and keratinocytes – to determine what distinguished them and find out what we would need to change to reprogram a type. of cell in the other.

We have identified 55 proteins, called reprogramming factors, potentially involved in the determination and maintenance of basal keratinocyte cell identity. We conducted additional experiments on each potential reprogramming factor and reduced the four-factor list that would transform mesenchymal cells into basal keratinocytes in vitro in Petri dishes. These keratinocytes then formed all the cells present in the new healthy skin.

We then tested the power of these four factors to treat cutaneous ulcers in mice. Only eighteen days after we applied a topical solution containing these four factors directly to the ulcers, we saw the healing occur. These four factors reprogrammed the mesenchymal cells of the wound into keratinocytes, which then developed into several types of cells that constitute healthy skin, closing and healing the wound. These cells continued to grow and join the surrounding skin, even in large ulcers. When we examined the mice three months and six months later, we saw that the newly generated cells functioned as healthy skin. The skin of rodents heals differently from human skin, so there was no visible scar tissue, even if it should have been there.

Further work is needed to ensure the safety of this approach, especially in the longer term, but as an initial test of the concept, the results are very promising.

We are optimistic that our approach represents a first proof of principle for the in vivo regeneration of an entire three-dimensional tissue, such as skin, and not just for individual cell types. In addition to healing wounds, our approach could be useful for repairing skin lesions, countering the effects of aging and helping us better understand skin cancer.

This article was originally published on The Conversation. Read the original article here: http://theconversation.com/new-technical-heals-wounds-with-reprogrammed-skin-cells-102715.