Biologists have created knockout stem cells without cilia

(ORDO NEWS) — Cilia, or cilia, are filamentous structures on the surface of cells that perform a number of important functions.

To investigate the role of cilia in the development of hereditary diseases like polycystic kidney disease, scientists created stem cells without these structures.

Cilia are tough, thin outgrowths located on the surface of most human cells, in particular the epithelium that lines the mucous membranes.

As a rule, they are able to move, making the so-called beats, and perform a number of important functions in the human body.

However, with 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 swollen 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 human pluripotent stem cells. Further, they were used as the basis for the creation of organoids – small similarities of organs consisting of the same cells. As a result, these mini-organs developed a condition similar to true ciliopathy.

“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.

We wanted to know if these cells could reproduce the symptoms of ciliopathies that also lack 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.

Biologists have created knockout stem cells without cilia
Polycystic kidney

Professor Friedman calls knockout stem cells without cilia very promising for the study of ciliopathy and the development of new methods for 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. So, polycystic kidney disease occurs in only one person out of 500.

Many ciliopathy have common symptoms, but 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 formation of tissues began, they seemed to just disintegrate,” Friedman adds.

“Though cells struggled to become something more complex. I think the takeaway here is that cilia help cells through the last stages of their development.”


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