Researchers here report an interesting application of in situ cell programming. Knowing that keratinocytes do a lot of the heavy lifting in the coordination of skin healing, they reprogrammed cells at the surface of non-healing wounds, transforming them into keratinocytes capable of guiding the regeneration of skin. This is thought to be a way to aid healing in older individuals, or in other cases where chronic inflammation disrupts the normal processes of regeneration. Certainly this approach is notable for regenerating the full structure of skin, something that has only been achieved by one or two other methodologies to date.
Scientists 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."
The scientists 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.
The researchers first compared the levels of different proteins of the two cell types (inflammatory versus 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 (known as 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. The researchers are planning more studies to optimize the technique and begin testing it in additional ulcer models.