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Published on : Oct 04, 2017

A key hurdle in the complete understanding of polycystic kidney disease (PKD), a life-threatening disease affecting humans, is the lack of human cellular models or organoids that can capture cystogenesis reliably. Probably for the first time, scientists have created a mini-kidney organoid and manipulated its environment to understand the progression of the disease accurately. A team of researchers from across various institutes and departments of the University of Washington (UW) School of Medicine, Seattle, U.S., showed that by systematically substituting certain physical components in the environment, the formation of cysts can be manipulated-increased or decreased-a result that will help in creating a robust model to reveal the secrets of PKD cystogenesis. The team was led by Benjamin Freedman from Division of Nephrology of the institute and was assisted by medical scientists from University of Toronto, Canada and Seattle Children’s Hospital, Seattle.

The methods, observations, and results were detailed in a paper published on October 2, 2017 in the journal Nature Materials.

Organoid Cystogenesis Critical in Understanding Disease Microenvironment

In earlier studies, the researchers have created a genetic model of PKD, made up of stem cells and derived kidney organoids. However, an accurate understanding of the cyst formation was not possible. The investigators resorted to removal of adherent cues and stoma and found that this triggers the production of cysts typical of PKD and results in the growth of PKD cell lines. The manipulation of the physical environment highlighted defects in polycystin-1 (PC1) expression, one of the key causes of the renal disease.

Manipulating Micro-Environment of Polycystin Proteins Key behind Renal Disease Control

In one of the experiments, the scientists found the addition of cyclic adenosine monophosphate (cAMP) can induce the growth of cysts in PKD mini-kidneys and its control organoids

One of the researchers found that polycystin proteins played the key role in PKD progression and opined that by manipulating their external mini-environment disease can be controlled.

The research will prove useful for medical scientist in aiding the development of robust models that will be further used to develop personalized therapies for various kidney disorders.