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Grow the skin you’re in: In vivo generation of chimeric skin grafts

Skin grafting is an essential procedure used to treat serious skin wounds. However, for extensive wounds, obtaining sufficient donor skin can be difficult, and generating artificial skin substitutes that include hair follicles and sweat glands and can be grafted into deep wounds has not been successful. Now, researchers in Japan report a new way to “grow your own” donor skin that could help improve the success of generating skin grafts.

In a study published last month in Nature CommunicationsResearchers at Tokyo Medical and Dental University (TMDU) have revealed that growing donor skin in another species produces surprisingly robust and functional skin grafts.

The gold standard for treating burn wounds is autologous skin grafting, a process in which sheets of skin containing both the epidermis (the outer layer) and the dermis (the deeper layer) are transferred from elsewhere. of the patient’s body to cover the injured area. . However, in the case of large wounds it may be difficult to obtain enough skin from limited donor sites. Split-thickness grafts containing primarily epidermis and only some dermis can be used to cover larger areas, but do not include features such as hair and sweat glands, and are more prone to shrinking and scarring.

“As alternatives to autologous skin grafts, artificial skin substitutes have been developed, including cultured epidermis and reconstituted skins,” says the study’s lead author, Dr. Hisato Nagano. “However, these options are inferior, as cultured epidermis can only be used for superficial wounds and the graft rate of reconstituted skins is low.”

To provide proof of concept for a new way to produce autologous skin grafts, the researchers generated skin grafts by introducing a mutation into mouse fetuses that prevented them from developing a mature epidermis. These fetuses were then injected with mouse stem cells and allowed to develop normally until birth, when their skin growth was analyzed.

“The results were very surprising,” explains Dr. Naoaki Mizuno, corresponding author. “Not only were the chimeric mice born covered with large patches of skin derived from the injected cells, but these patches also survived for up to 3 months when grafted onto mature mice, and even grew fur.”

Interestingly, injecting human skin cells into the same mutated mouse embryos produced similar results: as the mice developed in the wombThey grew sheets of human skin that mimicked the structure and organization of the mature epidermis.

“Our findings suggest that semiautologous skin grafts containing hair follicles and other skin appendages can be generated. live and successfully grafted,” says lead author Dr. Hiromitsu Nakauchi.

Since mouse embryos can only grow small amounts of skin, the next step would be to expand the process to larger animals with a longer gestation period to generate large human skin grafts. This approach, which involves generating only skin tissue, could help avoid ethical concerns about using human-animal chimeras to produce organs for medical use.