The Alchemy of Healing: Researchers Turn Open Wounds into Skin

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Plastic surgery to treat large cutaneous ulcers, including those seen in people with severe burns, bedsores or chronic diseases such as diabetes, may someday be a thing of the past. Scientists 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 and helping us to better understand 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,” says Salk Professor Juan Carlos Izpisua Belmonte, holder of the Roger Guillemin Chair and senior author of the new paper, published in the journal Nature on September 5, 2018. “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 image represents the first proof of principle for the successful regeneration of a functional organ (the skin) inside a mammal, by a technique known as AAV-based in vivo reprogramming. Epithelial (skin) tissues were generated by converting one cell type (red: mesenchymal cells) to another (green: basal keratinocytes) within a large ulcer in a laboratory mouse model.

Credit: Salk Institute

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.

Izpisua Belmonte and Salk Research Associate Masakazu Kurita, who has a background in plastic surgery, knew that a critical step in wound recovery was the migration–or transplantation–of basal keratinocytes into wounds. These stem-cell-like cells act as precursors to the different types of skin cells. But large, 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.

Izpisua Belmonte and Kurita wanted to directly convert these other cells into basal keratinocytes–without ever taking them out of the body. “We set out to make skin where there was no skin to start with,” says Kurita.Salk scientists develop new technique to heal large ulcers by reprogramming wound cells into skin cells. From left: Masakazu Kurita and Juan Carlos Izpisua Belmonte.