Skin for bald mice
Human skin and hair were grown in a Petri dish
Daria Spasskaya, N+1
American scientists have grown a piece of human skin in vitro from scratch from embryonic cells. The resulting organoid formed not only the main layers of the skin – the dermis and epidermis, but also hair follicles, from which, after transplanting a piece of mouse skin, hair grew. The work was published in Nature (Lee et al., Hair-bearing human skin generated entirely from pluripotent stem cells).
Figure from the press release of Oregon Health & Science University Hairy, lab-grown human skin cell model could advance hair loss research – VM.
The skin is a complex multi–layered organ, which in the process of embryogenesis consists of different germ leaves. The surface of the skin, or epithelium, originates from the ectoderm (from which the nervous system is also formed), and the deep layers of the skin (dermis), which contain vessels, glands and hair follicles, are of mesodermal origin. The complex structure and mixed origin makes it difficult to grow skin in vitro.
Laboratory-grown skin can be useful not only for scientists investigating its functioning, but also for patients suffering from burns, baldness and a number of more serious diseases. For example, we talked about epidermolysis bullosa, in which the skin literally peels off from the underlying structures. This disease is genetically determined, but the problem can be solved by transplanting healthy epithelium grown in the laboratory. In this case, scientists managed to restore the skin of a sick boy with the help of genetic modification and cultivation of his own epithelial cells.
In the new work, researchers from Boston Children's Medical Center, Harvard Medical School and Indiana University under the leadership of Karl Koehler was able to grow not just epithelium in a Petri dish, but a full-fledged multi-layered skin with glands, nerve endings and hair follicles. The basis for the organoid (organ in miniature) were pluripotent human stem cells, which were incubated with a complex cocktail of growth factors for several months.
The scheme of development of the cutaneous organoid. Here and below are the drawings from the article by Lee et al.
Embryonic cells formed a ball in the incubator, which, thanks to the artificial activation of some signaling pathways and blocking others, differentiated into keratinocytes (precursors of epidermal cells) and fibroblasts (precursors of dermis). It took two weeks. Two weeks later, melanocytes (producing melanin) and precursors of sensitive neurons appeared in the cell mass. On day 56, the rudiments of follicles appeared in the organoid. Finally, on day 140, the organoid turned into a small piece of almost full-fledged skin with hairs, sebaceous glands and fatty tissue.
This piece was planted with an immunodeficient mouse (such animals are used so that foreign organs are not rejected), and it took root normally. A study of the skin transcriptome from a test tube showed that it roughly corresponds to the fetal facial skin in the second trimester of pregnancy, and judging by the formed nerve cells, it should respond to touch.
The low rate of development means that lab-grown hairy skin is not suitable, for example, for emergency treatment of burns. However, as dermatologists joke from The University of Pennsylvania, who wrote an accompanying note in Nature, the authors of the work took another step forward in the treatment of baldness in mice. On this occasion, it is worth mentioning the work of two years ago, in which Japanese scientists described a high-performance method of growing hair follicles separately from the skin. Follicle precursors were also successfully transplanted into mice.
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