Acute Kidney Injury (AKI) is the rapid loss of kidney function, with death rate of more than 60 percent among intensive care patients. Using induced pluripotent stem cells (iPSC) has been found to be more successful than conventional methods for treating AKI. Professor Kenji Osafune and his team of researchers at Centre for iPS Cell Research and Application (CiRA) at Kyoto University worked with scientists from Astellas Pharma Inc., to develop a protocol that used kidney progenitor cells to form structures that resembled proximal renal tubules.
During kidney organogenesis, Osr1 and Six2 transcription factors interact to maintain kidney nephron progenitor status. In addition, the combination of Osr1 and Six2 is used as a specific marker for nephron progenitors. The researchers were able to differentiate human iPSCs into renal progenitors, marked by Osr1 and Six2. In vitro and in vivo, these renal progenitors developed into proximal tubule-like structures.
In a mouse model that used ischaemia and reperfusion to induce AKI, transplantation of these renal progenitor cells to the mouse kidney substantially reduced the rise in urea nitrogen and creatinine levels in the blood, and attenuated histopathological changes including tubule dilatation with casts, tubular necrosis, and interstitial fibrosis. The researchers concluded that the trophic factors secreted from the renal progenitor cells provided the protective effects, as there was no engraftment of these transplanted renal progenitors.
This groundbreaking research shows that cell therapy with renal progenitor cells derived from human-iPSCs could become a therapeutic option for patients suffering from AKI, by minimising renal tissue damage and preventing acute kidney damage from developing into chronic kidney problems. CiRA and Astellas also plan to develop novel cell-based therapies for chronic kidney disease (CKD).
Original paper can be accessed here.