Renal stem cells in recovery from acute kidney injury.

The kidney has a dramatic capacity to regenerate after injury. Whether stem cells are the source of the epithelial progenitors replacing injured and dying tubular epithelium is currently an area of intense investigation. Studies from our laboratory and others have supported a model whereby many surviving renal epithelial cells after injury become dedifferentiated and take on mesenchymal characteristics. These cells proliferate to restore the integrity of the denuded basement membrane, and subsequently redifferentiate into a functional epithelium. An alternative possibility is that a minority of surviving intratubular cells possess stem cell properties and selectively proliferate after damage to neighboring cells. Some evidence exists to support this hypothesis but it has not yet been rigorously evaluated. A third hypothesis is that extratubular cells contribute to repair of damaged epithelium. Bone marrow-derived stem cells have been proposed to contribute to this process but our work and work of others indicates that the vast majority of tubular cells derive from an intrarenal source. Recent evidence suggests that interstitial cells may represent another extratubular stem cell niche. The fundamental unanswered questions in this field include whether renal stem cells exist in the adult, and if they do where are they located (interstitium, tubule, cortex, medulla) and what markers can be relied upon for the isolation and purification of these putative renal stem cells. In this review we focus on our current understanding of the potential role of renal and extrarenal stem cells in repair of the adult kidney and highlight some of the controversies in this field.