Hairy skin from stem cells – Wissenschaft.de

The skin is an extremely complex organ – and therefore difficult to cultivate. But now researchers have succeeded in creating human skin and hair from stem cells in the laboratory. From the still undifferentiated starting cells, a rounded “organoid” first formed, then the different skin cell types and skin layers developed. In the experiment, the scientists were already able to transplant this skin to mice. This hairy “skin from the Petri dish” could be an important step for the healing of burn victims, but maybe also for bald heads.

Scientists have already managed to grow a whole range of tissues and organs in the laboratory, including miniature versions of the heart, kidneys or even the brain. However, human skin has been causing greater difficulties so far – mainly because of its great complexity. It comprises three different tissue layers, each with very different tasks and cell components. Hair follicles, sweat glands, nerve endings and blood vessels are also embedded in it. In the embryo, these cells and layers of tissue partially form different predecessor cells, which makes cultivation in the laboratory more difficult. Nevertheless, a team of researchers succeeded for the first time in 2016 in creating a complete skin including hair from the stem cells of mice. However, proof that this also works with human stem cells and thus human skin was still pending.

From stem cells to layered skin organoid

Jiyoon Lee from Harvard Medical School in Boston and his colleagues are now providing this evidence. They have grown almost complete human skin including hair follicles, sebaceous glands and nerve cells from stem cells and successfully transplanted them to mice. “This is the first study to show that human hair can also be grown from stem cells in a petri dish – this has been a goal of skin biologists for decades,” explains Lee’s colleague Karl Koehler. The starting point of the experiment was embryonic human stem cells that still have the ability to develop into almost all cell types in the body – they are pluripotent. The researchers placed these stem cells in a special nutrient solution, to which they added various growth factors in succession. First there were messenger substances that triggered the differentiation of the stem cells into the epidermis and their cell types, followed by growth factors that promoted the development of the dermis (dermis) and its structures.

After about 70 days, a roundish lump had grown from the cell culture, which already consisted of the epidermis, dermis and subcutaneous fat. In the course of the following weeks, the first hair follicles from which hair sprouted then developed in this organoid. “When the hair follicles grow, the hair roots first protrude outwards from the organoid in a radiation pattern,” explains Koehler. “It looks bizarre, almost a bit like a deep-sea creature with tentacles.” As the sequence progressed, these hair follicles also developed pigments and arranged at a relatively regular distance from one another. At the same time, some stem cells differentiated into nerve and sensory cells. “From day 125, these neuronal processes grew to the epithelium and wound around the hair follicles, similar to the immature nerve endings of a human fetus at 18 weeks,” the researchers report. Genetic tests showed that the gene activity of the various cells in these skin organoids was similar to that of the fetal skin.

Transplant to mice successful

“With this we have developed a culture system for organoids that can produce complex human skin from pluripotent stem cells,” said Lee and his colleagues. In order to test whether these skin organoids also become permanently viable skin, they planted mice small pieces of this layered skin on mice. Before this transplant, the immune system of the mice was severely restricted so that there was no rejection of the human tissue. After a short time, the pieces of skin had grown in and matured into real skin. In 55 percent of the grafts, the hair follicles remained intact and produced growing hair, as the researchers report. “Our results demonstrate that cystic skin organoids can unroll and become flat skin, for example, at a wound site,” said Lee and his team.

If the skin grafts remain successfully ingrown and regenerate in the long term, such a “skin” could offer completely new opportunities for the treatment of skin injuries and skin diseases. “This could change the way we approach many wounds and plastic reconstructions,” said Indiana University co-author Taha Shipchandler. “That would have a profound effect on this area of ​​medicine.” Leo Wang and George Cotsarelis of the University of Pennsylvania in Philadelphia see it similarly. In an accompanying comment, they write: “The study by Lee and colleagues is a big step towards a ‘cure’ for baldness in humans and it paves the way to other, even greater therapeutic options.” It is now important to optimize the method to be able to perform this skin cultivation with induced stem cells generated from adult cells. Because embryonic stem cells are ethically controversial and only available to a limited extent.

Source: Jiyoon Lee (Harvard Medical School, Boston) et al., Nature, doi: 10.1038 / s41586-020-2352-3

June 5, 2020

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