Smoker on a chip
Stem Cell Vocal Cord Model made to suffer from tobacco smoke
Scientists have grown vocal cord tissue from human stem cells. Unlike the previous method, the new one does not require the use of dead donor cells, and the created tissue resembles the real one not only in cellular composition and functions, but also in response to irritating factors, for example, tobacco smoke. The work was published in the journal Nature Communications (Lungova et al., Human induced pluripotent stem cell-derived vocal fold mucosa mimics development and responses to smoke exposure).
It is very difficult to grow a human vocal cord model in vitro. The fact is that the ligaments are covered with a mucous membrane, which is very poorly restored. Therefore, it is impossible to obtain a sample of healthy cells from a living person. At the same time, in the absence of a cellular model, it is impossible to test drugs that could help people cope with inflammation of the ligaments and restore the voice.
Vlasta Lungova from the Wisconsin Institute of Medical Research and her colleagues have created a universal cellular model of the vocal cords. As a basis, they took the cells of the connective tissue of the vocal cords fibroblasts – their culture has existed for a long time, because they reproduce well.
Then the scientists took induced pluripotent human cells and developed a protocol by which they differentiated them into mucosal cells. To distinguish mucosal cells from fibroblasts, they were labeled with a green fluorescent protein. Then the new cells were planted on top of a connective tissue substrate: a two-layer structure was obtained, which was supposed to mimic the tissue of the vocal cords.
The researchers confirmed that their model reproduces the properties of a real mucous membrane: the cells of the deep layers were cubic in shape, and the cells on the surface became flat, as it should be in a multilayer epithelium. They expressed characteristic markers, and also produced mucin proteins, which make up an essential part of mucus.
Finally, the scientists tried to recreate the effect of mucosal damage on the resulting model. To do this, they cultured the cells for a week in the presence of a five percent extract of tobacco smoke. As a result of this effect, the mucosa became thinner, the cells began to keratinize (accumulate keratins), produce fewer mucins and more pro–inflammatory proteins - the same thing happened as with the vocal cords of smokers.
A model of the vocal cords of a healthy person (a) and the vocal cords of a smoker (b).
Thus, the new model turned out to be quite suitable for studying the structure of healthy and damaged vocal cords. In addition, induced pluripotent cells are easy to extract and grow the mucous membrane anew. This distinguishes the new model favorably from the old ones, which used dead donor cells or laryngeal fragments removed during operations.
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