Abstract
Acute kidney injury (AKI) is a public health problem worldwide. Several therapeutic strategies have been made to accelerate recovery and improve renal survival. Recent studies have shown that human adult renal progenitor cells (ARPCs) participate in kidney repair processes, and may be used as a possible treatment to promote regeneration in acute kidney injury. Here, we show that human tubular ARPCs (tARPCs) protect physically injured or chemically damaged renal proximal tubular epithelial cells (RPTECs) by preventing cisplatin-induced apoptosis and enhancing proliferation of survived cells. tARPCs without toll-like receptor 2 (TLR2) expression or TLR2 blocking completely abrogated this regenerative effect. Only tARPCs, and not glomerular ARPCs, were able to induce tubular cell regeneration process and it occurred only after damage detection. Moreover, we have found that ARPCs secreted inhibin-A and decorin following the RPTEC damage and that these secreted factors were directly involved in cell regeneration process. Polysaccharide synthetic vesicles containing these molecules were constructed and co-cultured with cisplatin damaged RPTECs. These synthetic vesicles were not only incorporated into the cells, but they were also able to induce a substantial increase in cell number and viability. The findings of this study increase the knowledge of renal repair processes and may be the first step in the development of new specific therapeutic strategies for renal repair.
Highlights
Most cases of Acute kidney injury (AKI) arise from renal ischemia, drug toxicity or metal exposure
Recent studies indicate that the predominant mechanism of repair after ischemic renal tubular injury is the regeneration by surviving tubular epithelial cells[8], suggesting that adult renal CD133+/CD24+ progenitor cells (ARPCs) could contribute to renal regeneration by means of paracrine/endocrine mechanisms
We found that the renal proximal tubular epithelial cells (RPTECs) and the glomerular ARPCs (gARPCs) were very susceptible to cisplatin, whereas the tubular ARPCs (tARPCs) were more resistant (Fig. 2E)
Summary
Most cases of AKI arise from renal ischemia, drug toxicity or metal exposure. Cisplatin is a widely used cancer chemotherapeutic agent that gives renal damage. Recent studies indicate that the predominant mechanism of repair after ischemic renal tubular injury is the regeneration by surviving tubular epithelial cells[8], suggesting that ARPCs could contribute to renal regeneration by means of paracrine/endocrine mechanisms. These cells have a multipotent differentiation ability, including the capacity to differentiate in tubular epithelial cells, osteogenic cells and adipocytes[9,10,11]. Other similar studies showed that unipotent singly fated clones constantly maintain and self-preserve the renal mouse kidney tissue throughout life and have renal progenitor characteristics After kidney damage, these precursors are activated by WNT signals and are able to regenerate new collective ducts or proximal tubules segments through the expansion of single clones[14]. All these studies agree that CD133+/CD24+ cells have high regenerative and reparative phenotype with an important role in the setting of renal damage repair
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