Potential roles of bone marrow–derived cells in renal protection/repair. After ischemic injury, the brush border of proximal tubular cells is rapidly lost, followed by either dedifferentiation and proliferation of these cells or cell detachment and death due to necrosis or apoptosis. The observation that the initial decline in renal function following ischemic injury is markedly diminished in animals receiving large numbers of MSCs suggests that these cells act to prevent the acute phase of the injury either by directly inhibiting cell death and/or by preventing inflammatory cell influx (I). Once injury has occurred, repair of the tubule requires the dedifferentiation, migration, and proliferation of the surviving tubular cells. In addition, it has been proposed that resident renal stem cells participate in the reparative phase by migrating into the tubule and differentiating into epithelial cells (14). MSCs may direct this phase of tubule repair by secreting a factor (or factors) that promotes tubular cell dedifferentiation and proliferation or by stimulating the influx of resident stem cells (II). A second bone marrow cell type, possibly HSCs, appears to serve as a reservoir of endothelial progenitor cells, which potentially promotes endothelial repair and increases renal medullary blood flow (III). Finally, the possibility remains that bone marrow–derived cells can, very rarely, undergo differentiation into or fuse with existing tubular cells to directly participate in tubule repair. The infrequent occurrence of these last 2 processes suggests that they are not critical for functional recovery from acute ischemic renal injury.