The kidney stroma in development and disease

The kidney is one of the most complex organs in the body. It is made up of thousands of patterned epithelial and endothelial tubules that work together to maintain body chemistry. Precise spatial integration of these different cell types is essential for the organ to function optimally. A complex and heterogeneous network of cells collectively referred to as 'stroma' lies between the epithelial and endothelial tubules. A growing body of evidence suggests that the stroma mediates communication between the epithelia and endothelia, and functions to support a variety of processes during kidney development and in the adult kidney, with implications for disease. However, stromal cells remain far less well defined than the epithelia and endothelia, and we understand only a fraction of their functions, leading some to refer to the stroma as the 'dark matter' of the kidney. In this Review, we discuss the developmental origins of the stroma and describe current understanding of its roles in the growth and patterning of the renal epithelia and endothelia, and in the maintenance and repair of the adult organ. Finally, we highlight critical questions that remain unanswered and the resources that will be required to answer them so that we can fully understand the function of these enigmatic cells.