It’s enough to give members of the transplant community goose bumps—and other features of the skin’s integumentary system. According to a new study, lab-grown skin needn’t be limited to plain, featureless sheets. This study, from scientists based at the RIKEN Center for Developmental Biology, indicates that lab-grown skin can be studded with hair follicles and sebaceous glands. When such skin is used as transplant tissue, it becomes better integrated with natural tissue, forming connections with nerves and muscles, including arrector pili muscles.
The advance was described April 1 in the journal Science Advances, in an article entitled, “Bioengineering a 3D Integumentary Organ System from iPS Cells Using an In Vivo Transplantation Model.” As the article’s title indicates, the advance relies, in large part, on the use of induced pluripotent stem (iPS) cells.
Cells were taken from mouse gums and treated with chemicals to transform them into iPS cells. In culture, the cells properly developed into what is called an embryoid body (EB)—a three-dimensional clump of cells that partially resembles the developing embryo in an actual body.
The RIKEN-based team, led by Takashi Tsuji, Ph.D., created EBs from iPS cells using Wnt10b signaling and then implanted multiple EBs into immune-deficient mice, where they gradually changed into differentiated tissue, following the pattern of an actual embryo. Once the tissue had differentiated, the scientists transplanted them out of those mice and into the skin tissue of other mice, where the tissues developed normally as integumentary tissue, the tissue between the outer and inner skin that is responsible for much of the function of the skin in terms of hair shaft eruption and fat excretion.
“This bioengineered 3D integumentary organ system was fully functional following transplantation into nude mice and could be properly connected to surrounding host tissues, such as the epidermis, arrector pili muscles, and nerve fibers, without tumorigenesis,” wrote the authors of the Science Advances article. “The bioengineered hair follicles in the 3D integumentary organ system also showed proper hair eruption and hair cycles, including the rearrangement of follicular stem cells and their niches.”
The authors noted that potential applications of the 3D integumentary organ system include in vitro assay systems, animal model alternatives, and bioengineered organ replacement therapies. They also explained the importance of using the signaling molecule Wnt10b: “…the frequency of hair follicle formation, but not epithelial tissue formation, in in vivo explants was controlled by Wnt10b signaling in EBs. After treatment with Wnt10b on day 6 in culture, we detected the expression of neural crest markers, including Nestin, Pax3, Snail, and Twist. Therefore, our findings suggest that Wnt10b signaling plays important roles in the formation of hair follicles in the skin field, neural crest–derived melanocyte differentiation, and progression of organogenesis through reciprocal epithelial-mesenchymal interactions during morphogenesis.”
“Up until now, artificial skin development has been hampered by the fact that the skin lacked the important organs, such as hair follicles and exocrine glands, which allow the skin to play its important role in regulation,” said Dr. Tsuji. “With this new technique, we have successfully grown skin that replicates the function of normal tissue. We are coming ever closer to the dream of being able to recreate actual organs in the lab for transplantation, and also believe that tissue grown through this method could be used as an alternative to animal testing of chemicals.”