Generating "mini-kidney" structures from human stem cells may lead to much-needed therapies for kidney disease
Diseases affecting the kidneys represent a major and unsolved health issue worldwide. The kidneys rarely recover function once they are damaged by disease, highlighting the urgent need for better knowledge of kidney development and physiology.
Researchers led by Juan Carlos Izpisua Belmonte, who holds the Roger Guillemin Chair, have now developed a novel platform to study kidney diseases. For the first time, they have generated three-dimensional kidney structures from human stem cells, opening new avenues for studying the development and diseases of the kidneys and for discovering new drugs that target human kidney cells to help restore kidney function. The findings were reported in Nature Cell Biology.
Scientists had created precursors of kidney cells using stem cells as recently as last summer, but Izpisua Belmonte's team was the first to coax human stem cells into forming three-dimensional cellular structures similar to those found in kidneys. Their findings demonstrate for the first time that pluripotent stem cells (PSCs)—cells capable of differentiating into the many cells and tissue types that make up the body—can be made to develop into cells similar to those found in the ureteric bud, an early developmental structure of the kidneys, and then can be further differentiated into three-dimensional structures in organ cultures. The scientists accomplished this with both human embryonic stem cells and induced pluripotent stem cells (iPSCs), human cells from the skin that have been reprogrammed into their pluripotent state.
After generating iPSCs that demonstrated pluripotent properties and were able to differentiate into mesoderm, a germ cell layer from which the kidneys develop, the researchers made use of growth factors known to be essential during the natural development of kidneys to culture both iPSCs and embryonic stem cells. This was sufficient to commit the cells toward progenitors that exhibited clear characteristics of renal cells in only four days.
Izpisua Belmonte's team also tested their protocol on iPSCs from a patient clinically diagnosed with polycystic kidney disease (PKD), a genetic disorder characterized by multiple, fluid- filled cysts that can lead to decreased kidney function and kidney failure. They found their methodology could produce kidney structures from patient-derived iPSCs. Because of the many clinical manifestations of the disease, neither gene- nor antibody-based therapies are realistic approaches for treating PKD. Izpisua Belmonte's technique might help circumvent this obstacle and provide a reliable platform for pharmaceutical companies and investigators studying drug-based therapeutics for PKD and other kidney conditions.