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STELLAR – Stem Cells in Kidney Disease – Stem Cell based …

July 12th, 2015 7:45 pm

Stem Cells in Focus is an ISSCR topic in which a series of webcasts is organized allowing the public to discuss Stem Cell topics with leaders in the field.

Yesterday STELLAR member Melissa Little dicussed her topic during a webcast session on:Exploring Organoids: Growing a Kidney in a Dish.

Below is an interview with Melissa conducted byMaya Chaddah leading up to the webcast.

There was great excitement in 2013 when Australian scientist, Prof. Melissa Little, at The University of Queenslands Institute for Molecular Bioscience in Brisbane, Australia saw tiny buds of tissue growing in a dish that looked like embryonic kidneys. Originally a cancer geneticist, she had spent years studying the genes and pathways that lead to the formation of Wilms tumor, a kidney cancer found in children. As the connections between abnormal kidney formation during development and kidney dysfunction in children became apparent, she began exploring new ways to help individuals with kidney disease.

In the 15 years since Prof. Little started focusing on kidney development, renal disease and repair, the rates of chronic kidney disease have skyrocketed globally, due in large part to conditions like diabetes, hypertension (high blood pressure), glomerulonephritis (immune-mediated disease) and cardiovascular disease. Although the adult kidney can repair some damage for example, after a night of excessive alcohol, a period of dehydration, rapid blood loss, or exposure to chronic toxins it cannot grow new nephrons, which are vital to its function, after we are born. So chronic kidney damage takes its toll and ultimately leaves individuals on dialysis or awaiting kidney transplants, which are in very short supply.

The kidney is a very complex organ, comprised of 250,000 to 2 million nephrons that filter the blood (about 5 cups/minute), resorb nutrients and excrete waste. Each nephron is shaped like the head of a wrench leading into a long convoluted tube that bends and winds. Blood is filtered at the head of the wrench and different points along the tube take back what the body needs ions, amino acids and water. The tube then dumps what the body doesnt want into a large pipe called the collecting duct, which funnels the waste to the bladder for excretion. Any condition that repeatedly affects the ability of the nephrons to filter the blood can lead to a build-up of kidney damage over time.

Prof. Littles team was keen to understand kidney development in humans. Because the adult human kidney cannot make new nephrons, they attempted to replicate the process by which nephrons develop in the human embryo, using cultured cells grown in the laboratory. This involved identifying the conditions under which embryonic stem cells derived from the earliest unspecialized cells in an embryo can be coaxed to make mesoderm, the layer of cells in the early embryo with the potential to make kidney cells. From there, they developed a very tight, quality controlled method for reproducibly making nephron progenitors, the cells which make nephrons, as well as early nephrons and collecting duct cells.

What Prof. Littles team finds amazing is how exactly these types of cells, the nephrons and their progenitors and collecting duct cells, self-assemble into three dimensional structures outside the body, in a totally artificial lab environment. She likens the mystery to when animals are born and immediately just know how to stand up and go to their mothers. The kidney organoids her team can grow right now are only tiny buds of tissue, much smaller than normal kidneys and less complicated, but clearly with the same kinds of cells found in an embryo making a kidney. The next steps are to keep pushing the kidney organoids down the developmental pathway that ends with fully functional organs, and then to investigate whether the nephrons could do their job if given a blood supply.

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