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Researchers at the Salk Institute have developed a technique to directly convert the cells in an open wound into new skin cells. The approach relies on reprogramming the cells to a stem-cell-like state and could be useful for healing skin damage, countering the effects of aging. This is 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.
Cutaneous ulcers- wounds that can extend through multiple layers of the skin are typically treated surgically, by transplanting existing skin to cover the wound. However, when the ulcer is especially large, it can be difficult for surgeons to graft enough skin. In these cases, researchers are able to isolate skin stem cells from a patient, grow them in the lab and transplant them back into the patient. However, such a procedure requires an extensive amount of time, which may put the patient’s life at risk and is sometimes not effective.
Severe wounds that have lost multiple layers of skin no longer have any basal keratinocytes. And even as these wounds heal, the cells multiplying in the area are mainly involved in wound closure and inflammation, rather than rebuilding healthy skin. The researchers compared the levels of different proteins of the two cell types (inflammation and keratinocytes) to get a sense of what they’d need to change to reprogram the cells’ identities.
They pinpointed 55 “reprogramming factors” (proteins and RNA molecules) that were potentially involved in defining the distinct identity of the basal keratinocytes. Then, through trial and error and further experiments on each potential reprogramming factor, they narrowed the list down to four factors that could mediate the conversion to basal keratinocytes.
When the team topically treated skin ulcers on mice with the four factors, the ulcers grew healthy skin called epithelia within 18 days. Over time, the epithelia expanded and connected to the surrounding skin, even in large ulcers. At three and six months later, the generated cells behaved like healthy skin cells in a number of molecular, genetic and cellular tests.