According to a recent article, scientists were able to create cilia-free stem cells that may help in finding the causes of cilia-linked illnesses such as polycystic kidney disease.
Polycystic kidney disease is characterized by cysts that develop in the kidneys and affect their ability to filter waste from the blood. These cysts can lead to kidney failure due to the enlargement of the organ. While it mainly affects the kidneys, other organs may also feel the effects, with the liver being the most common. About 500,000 people have this disease in the United States.
This disease comes in two different forms: autosomal dominant (ADPKD) and autosomal recessive (ARPKD).
Symptoms
The main symptom of this disease is cysts. Other symptoms include high blood pressure, pain in the sides and back, blood in the urine, recurring urinary tract infections, kidney stones, headaches, a feeling of fullness in the abdomen, kidney failure, and abnormalities within the heart valve. Those who have polycystic kidney disease are at a higher risk of aneurysms, which can be life-threatening.
Cause
There are multiple genes that connect to this disease. Mutations in the PKD1, PKD2, and PKHD1 genes can all cause polycystic kidney disease. The mutations in the PKD1 and PKD2 genes are inherited in an autosomal dominant pattern, while the mutation of the PKHD1 gene is inherited in an autosomal recessive pattern. The exact functions of these genes are unknown, but it is suspected that they help to transmit chemical signals from outside of the cell to the nucleus.
Despite the majority of cases of this disease being inherited, a small portion of cases are not caused by gene mutations. In these cases people often have other forms of kidney diseases, and they have been treated with hemodialysis for multiple years.
Creating the Cilia-Free Stem Cells
Cilia are the tiny hairlike structures found on nearly every cell. The rare diseases that come from defects in the cilia are called ciliopathies, and unfortunately there is not much known about many of these diseases. As a result, a group of scientists decided to create an experiment where the cilia in normal human pluripotent stem cells were deleted. The results of this caused the human tissues and organoids created by the cilia-free stem cells to have ciliopathy-like symptoms. This proved that even when the cilia are removed from the stem cells, they will still re-create the symptoms of ciliopathy. Furthermore, when the cilia-free cells were turned into tissues and organoids, they re-created polycystic kidney disease and brain development issues.
Significance of This Discovery
These cilia-free stem cells, also referred to as cilia-knockout stem cells, provide scientists with a whole new tool for understanding and treating various ciliopathies. Since ciliopathies affect numerous organs and pluripotent stem cells can turn into any type of tissue within the body, these new cells can offer a simple way to investigate these diseases.
Another discovery scientists made through this experiment is that the cilia-free stem cells are not able to fully become a new form. This means that after turning into tissues, the cells break down and cannot reach their final developmental stages without cilia.
Now, scientists can start testing and comparing the molecular actions in the cilia. They will use a wide range of cell types, including those that are cilia-free and those that have cilia but do not have the PKD genes, to find out more about what is happening in the molecules. The hope is that this is a step towards finding out the particular disruptions in genetic molecules that then create polycystic kidney disease.
