While stem cells’ applications in regenerative medicine are now well documented, it was only in the early 1980s that their benefits for burn victims became apparent. In 1983, a tragic fire accident led to two extensively burnt young boys receiving the first grafts made of skin cultivated from stem cells in the USA.
Nearly four decades since that breakthrough, stem cells have become a mainstay in burn units across the world—but some limitations remain. “Nobody has been able to regenerate hair follicles, sebaceous glands and sweat glands,” said Yann Barrandon, visiting scientist at A*STAR’s Skin Research Institute of Singapore (SRIS). This could be due to several reasons, like the stem cells being restricted to certain lineages, lacking proper signaling, or both.
Now, along with A*STAR Research Fellow Jun-ichi Sakabe and Stéphanie Claudinot from the University of Lausanne and Ecole Polytechnique Fédérale Lausanne, Barrandon has shown that epithelial cells from distantly related organs can form the skin’s characteristic features.
First, the team took epithelial stem cells from different body parts of adult rats—including the esophagus, trachea, vagina, bladder, gut as well as foot pads among others—and allowed them to multiply in culture. The cells were then grafted onto the backs of newborn mice, where they were left to develop for several months.
As predicted, cells that shared the skin’s embryonic lineage like the footpad, oral cavity and sweat glands of the rat integrated well into the mouse epidermis, producing functional sebaceous glands and hair follicles.
But in an unexpected twist, the researchers discovered that even stem cells thought to be far removed from the skin, such as the rat’s prostate, vagina, bladder and esophagus, also contributed to the mouse pup’s developing fur.
Despite their differing lineages, one thing these stem cells all have in common is Tp63, a transcription factor considered to be a master gene for the development of the epidermis and its appendages, explained Barrandon. When exposed to the proper environment—like the newborn mice’s skin—cells that expressed Tp63 were able to cross lineage boundaries and contribute to the epidermis. On the other hand, gut cells, which do not express Tp63, were unable to integrate into the developing skin.
“We have now identified several sources of stem cells with skin-forming ability, some of them very accessible in a clinical set-up, such as the bladder,” Barrandon said. “The capacity to generate functional hair follicles and sebaceous glands will open new avenues in regenerative medicine of the skin, as well as in plastic, reconstructive and aesthetic surgery.”
The A*STAR-affiliated researchers contributing to this research are from the Skin Research Institute Singapore (SRIS).