Scientists create 'mini-kidneys' from human stem cells

Date: Nov-19-2013The US National Institute of Diabetes and Digestive Kidney Disease states that more than 20 million adults in the US have some form of chronic kidney disease, showing the need for better knowledge and treatment of the condition. Now, scientists have created miniature 3D kidney structures from human stem cells with the aim of providing just that.

Investigators from the Salk Institute for Biological Studies in California say the mini-kidney structures could open new avenues for studying the development of kidney disease and lead to the creation of new drugs that target the condition.

The researchers note that although scientists had previously created precursors of kidney cells using human stem cells this year, the team at Salk is the first to create 3D cellular structures that are similar to those found in human kidneys.

How were the 3D kidney structures created?

Scientists used mouse embryonic kidney cells (red) to 'coax' human stem cells to turn into early-stage uretic buds - early structures of the human kidney.
Image credit: Salk Institute for Biological Studies

The researchers explain that the 3D structures, the details of which are published in the journal Nature Cell Biology, demonstrate that pluripotent stem cells (PSCs) can be changed into cells similar to those found in the uretic bud - a structure found in the early development of kidneys.

These cells can then be made into 3D structures through organ culture.

The investigators say they were able to do this using both human embryonic stem cells and induced pluripotent stem cells (iPSCs) - human cells from the skin that have been "reprogrammed into their pluripotent state."

The research team created iPSCs that showed pluripotent properties and were able to "differentiate" into mesoderm - a germ layer from which the kidneys develop.

The scientists used growth factors known to play a part in the natural development of human kidneys in order to culture both iPSCs and embryonic stem cells.

They explain that the combination of signals from these growth factors, which they describe as molecules that "guide the differentiation of stem cells into specific tissues," were enough to "commit" the cells toward progenitors that demonstrated characteristics of kidney cells in 4 days.

By culturing these progenitor cells with kidney cells from mice, the researchers were able to create organ structures similar to structures found in the uretic bud.

The researchers say this demonstrates that the mouse cells were able to provide the "appropriate developmental cues," which allowed the human stem cells to turn into 3D kidney structures.

Explaining their findings further, senior study author Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory, says:

"Attempts to differentiate human stem cells into renal cells have had limited success.

We have developed a simple and efficient method that allows for the differentiation of human stem cells into well-organized 3D structures of the ureteric bud, which later develops into the collecting duct system."

3D structures made from patient-derived cells

The investigators tested their method on iPSCs from a patient who was clinically diagnosed with polycystic kidney disease (PKD) and discovered that they were able to create 3D kidney structures from these patient-derived cells.

PKD is a genetic form of kidney disease that is characterized by multiple cysts filled with fluid. The researchers explain that because of the symptoms of this disease, gene-based or antibody-based strategies are "not realistic" for treating the condition.

Therefore, they note that the 3D structures could be used in the testing of drugs to combat PKD and other diseases of the kidney.

"Our differentiation strategies represent the cornerstone of disease modeling and drug discovery studies," says lead study author Ignacio Sancho-Martinez.

"Our observations will help guide future studies on the precise cellular implications that PKD might play in the context of kidney development."

Earlier this year, Medical News Today reported on the creation of mini-brains grown from stem cells.

Written by Honor Whiteman

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