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A team formed by staff at the Hospital Clínic have discovered a method to create and maintain an unlimited number of nephron stem cells in the laboratory; nephrons being the basic functional unit of the kidney responsible for filtering the blood and the excretion of urine.

The study represents a springboard to developing new treatments for kidney disease, especially for people with renal insufficiency, to applying cell therapies to kidneys with gene defects and it opens up the possibility to create kidneys for transplantation in the long term.

The research study was led by Doctor Juan Carlos Izpisua Belmonte, professor of the Gene Expression Laboratory at the Salk Institute for Biological Studies in California, in collaboration with Doctor Josep Maria Campistol, CEO and nephrologist at the Hospital Clínic, and Marta Lazo, researcher at the August Pi i Sunyer Biomedical Research Institute (IDIBAPS). Researchers from the Universitat Catòlica de Murcia, the Clínica Cemtro in Madrid and the University of Tokai (Japan) also participated in the study.

The results, published in the journal Cell Stem Cell, show that for the first time it has been possible to preserve kidney stem cells (KSCs), which in the human body only exist during the first quarter of pregnancy, during which time the nephrons are formed. They later disappear, which is why adult kidneys, unlike the liver, are unable to regenerate themselves after damage or disease.

The researchers used embryonic KSCs and found that if these are left to grow in a three-dimensional culture instead of a one-dimensional, and if a new combination of signaling molecules is used, then the cells can survive for over 15 months. This is the first time this has been achieved, since the method had never been applied before.

In experiments with mice, the team observed that when they induced the cells to transform into nephron structures under these new conditions, they reacted as though they had always been there. According to the researchers, the creation of these KSCs which, once isolated, can be maintained in culture and used for future therapies– could be a starting point for growing functional organs in the laboratory.

The discovery could be important in the creation of transplantable kidneys, although this would require the cultivation of other types of stem cells essential for regenerating an entire kidney, which is where research is now headed. It could also be used to create other organ tissues by using the same three-dimensional culture from this study.

 

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