Researchers grow human skin on animals, showing
promise of approach to improve skin transplantation

Hiro Nakauchi, MD, PhD

July 23, 2024 - By Christopher Vaughan

Institute scientist Hiro Nakauchi and his colleagues have successfully grown full-thickness human skin on mice. If human skin can be grown on larger animals, the research could provide much needed skin transplants for human patients. The findings also may set the stage for first clinical application of human tissue grown in other animals to treat human disease. The research was published in the journal Nature Communications.

Skin transplants are required to treat a number of conditions, from treating severe burns to performing plastic surgery to alleviating genetic disorders like epidermolysis bullosa, the “butterfly disease” that makes skin so fragile that the slightest touch can result in sores and blisters. However, finding a source for skin transplants has been difficult. Skin can sometimes be harvested from one part of the body for transplant to another, but when it cannot, options are limited. Sheets of epidermis—the top layer of skin—can be grown in the lab, but when transplanted by itself, the results are not satisfactory because it lacks the dermis (the lower layer of skin) to support the epidermis.

“For deep wounds, we need both upper and lower layers of skin—both the epidermis and the dermis—to make skin with sweat glands and hair follicles,” Nakauchi said. Until now, scientists have been unable to grow full-thickness skin in the lab.

The recent research builds on Nakauchi’s efforts to grow human organs in farm animals as a way to address the shortage of organs available for transplantation. In that work, he and his colleagues are trying to insert human pluripotent cells into pig embryos that have been engineered to be unable to develop a heart.

The hope is that, as the pig embryo grows inside the mother pig, the human cells will become the heart that the pig cannot make. If the human cells are created from the patient who needs the heart, the resulting heart will be a perfect genetic match to the patient, lowering the risk of immune rejection. In the past, other researchers have implanted pig hearts in human patients, but this was not a long-term solution because the pig hearts were eventually rejected even under massive immunosuppression.

Although this groundbreaking project has been successful in studies using mice, rats and pigs, it has not yet been successful growing human skin in farm animals. The genetic gap between the two species is large, and human cells tend to be eliminated from the pig embryo before a heart develops. In the current research on skin, the researchers were able to bypass this roadblock because they injected skin precursor cells into the amniotic tissue at a later stage of development. “By bypassing the earliest stages of development, the skin cells were able to incorporate into the growing mouse,” Nakauchi said. “We were able to create full-thickness skin, with both dermis and epidermis, from the injected cells,” Nakauchi said.

The researchers now hope to try the same thing with pig embryos by injecting human skin precursor cells. “Because pigs are larger animals with longer gestation times than mice, we should be able to create skin sheets that we can transfer to patients,” Nakauchi said.

The researchers note that there would likely be some pig cells mixed in with the human skin grown on the pigs, creating some risk of immune rejection after transplantation. But Nakauchi says there are ways to address that issue. “We can use a strain of pig whose cells generate less of an immune response, and we may need to use some anti-rejection drugs for a while after transplantation,” he said. “But after some time, the immune system should eliminate the pig cells, leaving only human tissue, and we can stop immunosuppression.”

Nakauchi said he hopes that someday we won’t need animals to generate skin or other organs, but for now this is our best hope of providing effective treatments relatively soon. “We still have much to learn about developmental biology before we can grow fully-fledged organs in a dish. Hopefully, this research takes us one step closer.”

Nakauchi’s collaborators at the University of Missouri National Swine Resource and Research Center are currently developing pig embryos genetically unable to develop skin, which will pave the way for future research.

Clich here to learn more about the groundbreaking research being done in the Nakauchi lab.