For the first time, researchers have coaxed a primordial ball of cells into a multi-layered, transplantable patch of skin, sporting hair follicles and functioning glands.

The mouse-based study, published in Science Advances, brings scientists closer to pulling off the feat in humans, which would provide synthetic skin grafts that could treat burn victims and patients with various skin diseases. “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,” lead researcher Takashi Tsuji, of the RIKEN Center for Developmental Biology in Japan, said in a statement.

Researchers have been getting better and better and recreating tissues in lab—but for skin, they had gotten stuck at making simplified versions. Fully functioning skin includes three layers: the epidermis, an outermost protective layer that is mostly waterproof; the elastic dermis layer that gives skin flexibility as well as housing oil and sweat glands, hair follicles, nerve endings, and blood vessels; and the subcutaneous fatty layer that provides padding and insulation.

Growing all of the layers requires complex cell-to-cell interactions and self-organization. To pull it off in lab, Tsuji and colleagues first swiped cells from the gums of mice and used well-established protocols to revert them into a stem cell-like state—creating induced pluripotent stem cells (iPS cells). The researchers specifically engineered the cells to make a green fluorescent protein so the cells could be easily spotted.

Next, the researchers let the iPS cells grow for seven days, during which they formed “embryoid bodies”—balls of cells that resemble actual embryos that have precursors to multiple types of tissues. The researchers then implanted the cellular clumps into mice with deliberately weakened immune systems. There, the embryo-like balls peacefully began to mature into functional skin tissue without being attacked by immune cells. Key to this development, the researchers found, was the activation of cell signaling pathways called Wnt10b, which were known previously to be involved in organ development in embryos. In the study, researchers found that Wnt10b signaling led to more hair follicles in the fledgling skin tissue.

The researchers collected snippets of the implanted tissue and transplanted them onto the backs of hairless mice. On this second group of mice, the tissue acted like a normal skin, with tufts of black hairs sprouting out of the otherwise hairless mice. The tissue could secrete the oils that normal skin does, and it connected up with surrounding nerve and muscle tissue.

"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," Tsuji said. "With this new technique, we have successfully grown skin that replicates the function of normal tissue."

Next, the researchers will try to repeat the work using human cells to make furry skin patches fit for people.

Science Advances, 2015. DOI: 10.1126/sciadv.1500887 (About DOIs).