Tapping into the machinery of a cell and rewiring it to take on another identity is an exciting capability that scientists are really just beginning to explore. Already we've seen how this technology might turn skin cells into brain tumor predators, and how reprogrammed bone cells might give us the tissue regeneration abilities of a salamander. Now researchers at the Salk Institute report another groundbreaking advance in the area, converting open wounds into healthy skin without the need for surgery.
The work focuses on a type of wound known as cutaneous ulcers, which are long-lasting lesions commonly found on sufferers of severe burns, bedsores and diabetes. These complex wounds run deep, through several layers of skin, which often means that they need to be treated surgically by taking grafts of existing skin and layering them over the top.
With expertise in plastic surgery, Salk scientists Izpisua Belmonte and Masakazu Kurita started to explore advanced regenerative techniques that could avoid the need for these procedures. Key to their mission were cells called basal keratinocytes, which resemble stem cells in that they serve as a precursor to various types of skin cells.
In large and severe cutaneous ulcers, these basal keratinocytes are absent, while the cells that are present and multiply throughout the healing process focus their energies on closing the wound and curtailing inflammation, instead of regenerating healthy skin. So the scientists wondered, what if these cells could be recruited and used as basal keratinocytes?
"We set out to make skin where there was no skin to start with," says Kurita.
The team began by examining the levels of proteins in both types of cell and identified 55 proteins and RNA molecules unique to the basal keratinocytes. Through trial and error that number was whittled down to four, leaving the scientists with a neat set of "reprogramming factors," elements that could potentially be harnessed to give the cells a new identity.
These four factors were worked into a topical solution and used to treat mice with skin ulcers, who proceeded to grow healthy skin in just 18 days. Beyond that, the healthy skin expanded and melded with the healthy skin surrounding the wound and three to six months later, the reprogrammed cells behaved just like healthy skin cells in molecular, genetic and cellular tests.
Buoyed by these positive results, the team is now looking to optimize the technique and carry out more experiments to establish its long term safety. What's also impressive about this research is the fact that the cells could be converted while remaining in the body. Other promising examples of cell reprogramming have involved harvesting them from the body, engineering them in the lab and then injecting them back into the sample.
"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," says Salk Professor Juan Carlos Izpisua Belmonte, senior author of the new paper. "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."
The research was published in the journal Nature.
Source: Salk Institute
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