Researchers Program Open Wounds to Transform Into Skin

The novel technique that sees cells reprogrammed into stem-cell-like states has potential applications in wound healing, aging reversal and disease treatment.

In what may be this week's most impressive news, the Salk Institute of Biological Studies has revealed that its researchers have developed a technique for transforming wound cells into skin cells. The novel approach has potential applications in healing skin damage, fighting aging and even understanding skin cancer. 

"Our observations constitute an initial proof of principle for in vivo regeneration of an entire three-dimensional tissue like the skin, not just individual cell types as previously shown,” said Salk Professor Juan Carlos Izpisua Belmonte, senior author of the study. 

Reprogrammed into a stem-cell-like state

The process relies on the reprogramming of cells to a stem-cell-like state. Wound recovery relies heavily on the transplantation of basal keratinocytes, stem-cell-like cells that are predominant in the epidermis, into wounds.

These keratinocytes function as precursors to the different types of skin cells, leading to the skin reconstructing itself. However, large or severe wounds have lost the skin layers that carry basal keratinocytes, hindering the body's natural ability to heal itself.

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Whatever cells are left are focused on the more urgent life-saving tasks of wound closure and inflammation, so the process of rebuilding healthy skin is thwarted. But what if these remaining cells could be converted into basal keratinocytes? They could then proceed to restore the epidermis.

Belmonte and his team decided to develop a way to instigate such a reprogramming of cells into base keratinocytes that could happen directly on the wound. Their goal was essentially nothing short of attempting to engineer a skin-creating magic trick.

“We set out to make skin where there was no skin to start with,” said study co-author and Salk Research Associate Masakazu Kurita. 

Identifying reprogramming factors

They began by comparing the different protein levels of the two cell types (inflammation and keratinocytes) to identify the factors that made up the distinct identity of the basal keratinocytes. From there, they determined what they called “reprogramming factors” (proteins and RNA molecules) that could play a role in converting the cells.

Their initial assessment found 55 such elements. However, further research on each potential reprogramming factor was able to reduce that number to just four.

These final factors were the ones that could mediate the much-desired basal keratinocyte transformation, believed the scientists. Luckily, they were proven to be right.

Additional tests showed that skin ulcers on mice topically treated with these four factors exhibited a healthy regrowth of skin within a mere 18 days. This new skin, referred to as the epithelia, then proceeded to further expand and eventually merge with the surrounding undamaged skin.

More impressively, in only three to six months after the growth, the newly generated cells were found to behave like healthy skin cells in molecular, genetic and cellular tests. The team is now working to make their technique clinic-ready. 

“This knowledge might not only be useful for enhancing skin repair but could also serve to guide in vivo regenerative strategies in other human pathological situations, as well as during aging, in which tissue repair is impaired," said Belmonte.

The study was published in the journal Nature.

Via: Salk