The research opens new avenues for studying the development and diseases of the kidneys and may lead to new drugs that target human kidney cells.
Scientists had created precursors of kidney cells using stem cells recently, but the team led by Salk Institute for Biological Studies is the first to coax human stem cells into forming three-dimensional cellular structures similar to those found in our kidneys.
"Attempts to differentiate human stem cells into renal cells have had limited success," said senior study author Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and holder of the Roger Guillemin Chair.
"We have developed a simple and efficient method that allows for the differentiation of human stem cells into well-organised 3D structures of the ureteric bud (UB), which later develops into the collecting duct system," Belmonte said.
The 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 be further differentiated into three-dimensional structures in organ cultures.
UB cells form the early stages of the human urinary and reproductive organs during development and later develop into a conduit for urine drainage from the kidneys.
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 our kidneys for the culturing of both iPSCs and embryonic stem cells.
The combination of signals from these growth factors, molecules that guide the differentiation of stem cells into specific tissues, was sufficient to commit the cells toward progenitors that exhibit clear characteristics of renal cells in only four days.
The researchers then guided these cells to further differentiate into organ structures similar to those found in the ureteric bud by culturing them with kidney cells from
This demonstrated that the mouse cells were able to provide the appropriate developmental cues to allow human stem cells to form three-dimensional structures of the kidney.
The study is published in the journal Nature Cell Biology.