Ciliopathy in vitro
Biologists have created knockout stem cells without cilia
Mikhail Orlov, Naked Science
Cilia are rigid thin outgrowths located on the surface of most human cells, in particular the epithelium, which is lined with mucous membranes. As a rule, they are able to move, making so-called beats, and perform a number of important functions in the human body.
However, in some rare diseases, the so-called ciliopathies, there is a violation of the structure of the cilia and their work. Among them, polycystic kidney disease stands out, in which the shape of the renal tubules changes, and the kidney itself is covered with many cysts — cavities filled with fluid. Such "bubbles" develop from inflated and non-functioning tubules and gradually disrupt the functioning of neighboring, healthy ones.
In a new study, scientists knocked out, that is, removed, cilia from pluripotent human stem cells. Then they were used as a basis for creating organoids — small likenesses of organs consisting of the same cells. As a result, these mini-organs developed a condition similar to real ciliopathies.
"We are trying to figure out why cilia are needed, so we destroyed them in these cells," said Benjamin Freedman from the George Washington University School of Medicine (USA), one of the authors of a new publication in Nature Biomedical Engineering (Cruz et al., Modeling ciliopathy phenotypes in human tissues derived from pluripotent stem cells with genetically ablated cilia). — We wanted to find out if such cells can reproduce the symptoms of ciliopathies, in which there are also no cilia. Of course, when we turned these cells into tissues and organoids (tissue-like structures), they corresponded to polycystic kidney disease and brain development disorders."
Professor Friedman calls the knockout stem cells without cilia very promising for the study of ciliopathies and the development of new methods of their treatment. In addition to polycystic kidney disease, this group includes at least 14 genetic diseases. All of them belong to rare (so-called orphan) diseases. Thus, polycystic kidney disease occurs in only one person out of 500.
Many ciliopathies have common symptoms, but they can damage various organs to varying degrees: kidneys, brain, liver, retina, and so on. In addition, the pathology of the cilia is associated with developmental anomalies such as hydrocephalus, shortening of the ribs and the appearance of extra fingers.
Therefore, the obtained stem cells without cilia are a particularly valuable model system, because they allow us to study the most general and fundamental mechanisms of ciliopathies. Friedman and his colleagues managed to find out that cells deprived of these structures remain viable, but cannot change their shape.
"It was a surprise to me that at some point after the start of tissue formation, they seemed to simply disintegrate," Friedman adds. — Although the cells struggled to become something more complicated. I think the conclusion here is that the cilia help the cells go through the last stages of their development."
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