Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute Kidney Injury

Abstract

Human kidney is particularly susceptible to ischemia and toxins with consequential tubular necrosis and activation of inflammatory processes. This process can lead to the acute renal injury, and even if the kidney has a great capacity for regeneration after tubular damage, in several circumstances, the normal renal repair program may not be sufficient to achieve a successful regeneration. Resident adult renal stem/progenitor cells could participate in this repair process and have the potentiality to enhance the renal regenerative mechanism. This could be achieved both directly, by means of their capacity to differentiate and integrate into the renal tissues, and by means of paracrine factors able to induce or improve the renal repair or regeneration. Recent genetic fate-tracing studies indicated that tubular damage is instead repaired by proliferative duplication of epithelial cells, acquiring a transient progenitor phenotype and by fate-restricted clonal cell progeny emerging from different nephron segments. In this review, we discuss about the properties and the reparative characteristics of high regenerative CD133(+)/CD24(+) cells, with a view to a future application of these cells for the treatment of acute renal injury.

Keywords: acute kidney injury; regenerative medicine; renal progenitor cells; toll-like receptors.

FIG. 1.

Acute kidney injury causes cell apoptosis and necrosis at the proximal tubular level. Resident ARPCs (pink color) can participate in the repair process both directly, by means of their capacity to differentiate and integrate into the renal tissues, and indirectly, by means of paracrine factors capable to induce regeneration of the surviving tubular epithelial cells (blue color). The ARPCs could detect the injury by TLR2 that recognizes molecules derived from the injured tissue. The TLR2 activation could lead to the secretion of a series of chemokines that stimulate the proliferation of ARPCs themselves to increase the pool of resident cells. Other receptors on ARPCs, such as EGFR and IGF1R, could contribute to the cell activation in the repair process. ARPCs, adult renal stem/progenitor cells; RPT, renal proximal tubule.