Intravenous renal cell transplantation for acute kidney injury in rats

Acute kidney injury (AKI) contributes to greater mortality in clinical settings. The only available therapy is supportive and its efficacy is largely unpredictable. Multiple forms of therapy have been tried and stem cell therapy has resulted in some success, perhaps related to paracrine activation of renal recovery. In this work we tested the role of intravenous renal cell infusion with rat NRK52E cells (a poorly differentiated renal cell line) or with primary cells obtained from renal tubules of rat donors on AKI. The cells were reprogrammed to express the serum amyloid A1 gene (SAA1 is an acute phase protein) which is expressed in developing metanephric tubules and during the recovery stage of tubular injury. SAA1 also promoted functional tubulogenesis in NRK52E and in primary renal tubular cells. The SAA1 reprogrammed cells were always injected upon establishment of AKI. There were three models of AKI that dramatically improved by injections of NRK52E cells: gentamicin nephrotoxicity, cisplatin nephropathy, and ischemia‐reperfusion injury (IRI). The effects were detected within 48 hours post‐injection. We monitored cell engraftment after 7 days post‐injection and documented replacement of native injured cells with GFP (+) and SAA1 (+) donor NRK52E cells. Donor freshly isolated tubular cells were also reprogrammed with the SAA1 gene, cultured to expand cell number for one week, and then injected to rats with IRI. These renal cells also largely reversed renal dysfunction and were engrafted in damaged host tubules after 7 days. Control cells did not change AKI. We conclude that intravenous transplantation of SAA1 reprogrammed renal cells is effective in reversing the course of established AKI in the rat.