The FINANCIAL — Astellas Pharma Inc.and Prof. Osafune’s group of Center for iPS Cell Research and Application (Director: Dr. Shinya Yamanaka; “CiRA”), Kyoto University, as an achievement of their collaborative research for kidney regenerative medicine, published a research paper in “Stem Cells Translational Medicine” on line (9:00 EST, July 21).
New method for generating renal progenitors from human induced pluripotent stem cells (hiPSCs) was established;
Transplantation of human iPSC-derived renal progenitors ameliorated acute kidney injury (AKI) in mice;
Cell therapy using the hiPSC-derived renal progenitor cells could be developed for kidney diseases;
The research group found that transplantation of human iPSC-derived renal progenitors suppressed the renal dysfunction and histopathological changes associated with AKI in mice.
AKI is defined as a rapid loss of renal function resulting from various etiologies, with a mortality rate exceeding 60% among intensive care patients. Because conventional treatments have failed to alleviate this condition, a new innovative treatment option such as regenerative therapies is strongly anticipated. In this February, Italian research group reported that transplantation of human iPSC-derived renal progenitors via the tail vein ameliorated renal injury in a cisplatin-induced AKI mouse model, according to Astellas.
Transcription factors, Osr1 and Six2 interact synergistically to maintain nephron progenitor status during kidney organogenesis, and the combination of Osr1 and Six2 can be used as a specific marker set to define nephron progenitors. The research group has established a novel protocol to efficiently differentiate hiPSCs into OSR1+SIX2+ renal progenitors, and demonstrated the progenitors were able to form proximal renal tubule-like structures in vitro and in vivo. Moreover, in ischemia/reperfusion-induced AKI mouse model, renal subcapsular transplantation of these cells significantly suppressed the elevation of blood urea nitrogen and serum creatinine levels and attenuated histopathological changes, such as tubular necrosis.
This is the first report to demonstrate that the transplantation of renal progenitor cells differentiated from human iPSCs have therapeutic efficacy in the AKI mouse model induced by ischemia/reperfusion. No engraftment of transplanted renal progenitor cell indicates that trophic factors secreted from the cells exerted reno-protective effects on the host kidney.
These findings therefore suggest that cell therapy using hiPSC-derived renal progenitors might become one of therapeutic options for AKI patients by ameliorating renal tissue damage and possibly preventing transition to chronic tissue damage. Based on the findings, Astellas and CiRA will explore the possibility to develop new cell-based therapies for not only AKI but also chronic kidney disease (CKD).