AsianScientist (Nov. 9, 2018) – Scientists in Japan have used induced pluripotent stem (iPS) cells to develop kidney tissue that exhibits the early stages of congenital kidney disease. Their findings are published in Stem Cell Reports.
The kidneys are organs that filter out and discharge waste products from the blood. During this process, proteins in the blood should not leak into the urine. The membrane responsible for this filtration is part of a structure in the kidney known as the glomerular podocyte, which expresses a protein called nephrin.
If there is a genetic mutation affecting nephrin, a large amount of protein in the blood can leak into the urine, a classical symptom of congenital nephrotic syndrome. Clinicians find it difficult to treat this syndrome, and the absence of a technique to reproduce a mutated filtration membrane has hindered research progress.
In this study, scientists led by Professor Ryuichi Nishinakamura of Kumamoto University, Japan, have devised a way to mimic congenital nephrotic syndrome in the lab. First, they established iPS cells from the skin cells of a patient with congenital nephrotic syndrome who had a single nephrin mutation. When they induced these iPS cells to form kidney tissue in vitro, they found that nephrin, which should exist on the surface of the glomerular podocyte, remained inside the cell, and that almost no filtration membrane precursor could develop.
When the cells were transplantated into mice, nephrin, which typically moves toward the blood vessel side of normal podocytes, again remained inside the patient-derived cells. In other words, the initial pathology of this congenital kidney disease was reproduced by the iPS cells derived from the diseased patient.
Furthermore, when the nephrin mutation in patient-derived iPS cells was repaired and then induced to form kidney tissue, the abnormalities were normalized. Hence, the researchers concluded that this single nephrin mutation is responsible for causing congenital nephrotic syndrome, and that the disease could possibly be treated by repairing the mutation.
“Because we can now reproduce the pathology of congenital nephrotic syndrome, it should be much easier to explore therapeutic drugs using this podocyte,” said Nishinakamura.
“If a medication is discovered that controls [the expression of] nephrin protein, there is a strong possibility that it will be highly effective for treating kidney disease. What we have achieved here is a step towards the development of drugs that act on podocytes and reduce proteinuria.”
The article can be found at: Tanigawa et al. (2018) Organoids from Nephrotic Disease-Derived iPSCs Identify Impaired NEPHRIN Localization and Slit Diaphragm Formation in Kidney Podocytes.
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Source: Kumamoto University; Photo: Shutterstock.
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