The Regenerative Potential of Human Adult Renal Stem/Progenitor Cells

The human adult renal stem/progenitor cells (ARPCs) play a role in renal regeneration in two ways: by differentiating directly or by secreting reparative molecules. They can differentiate into epithelial, endothelial, osteogenic, and adipogenic cells. ARPCs can regenerate long segments of renal tubules and also missing podocytes in cortical nephrons after acute kidney injury (AKI). These renal progenitors express the Toll-Like Receptor 2 (TLR2); they are activated by TLR2 ligands and can secrete restorative and therapeutic factors capable of repairing renal tubular cells damaged. The TLR2 can act as a damaged sensor, and its activation can cause stem cell proliferation and differentiation, among other things. Kidney progenitors can repair physical and chemical damage, such as a wound in epithelial tissue or damage caused by cisplatin, a widely used chemotherapy drug that can cause nephrotoxic side effects. Following renal tubular cell damage, ARPCs release inhibin-A and decorin, which are directly involved in cell regeneration. The ARPCs can also prevent endothelial dysfunction and protect the endothelial compartment following exposure to lipopolysaccharides (LPS), thus promoting kidney repair. They exert an anti-fibrotic effect through the secretion of antiseptic molecules CXCL6, SAA4, and BPIFA2. Moreover, ARPCs possess immunomodulatory capabilities towards CD3+ CD4-CD8- (double negative; DN) T-lymphocytes and can promote regulatory T lymphocytes (Treg). In addition, it has been discovered that renal progenitors, thanks to the high expression of HOTAIR, can secrete high quantities of α-Klotho, an anti-aging protein capable of influencing the surrounding tissues and therefore modulating renal aging. These data open new perspectives on treating diseases, suggesting an underestimated role of ARPCs in preventing and repairing kidney injuries and novel strategies to protect the endothelial compartment and promote kidney repair.