iPSC technology-based regenerative medicine for kidney diseases

Abstract

AbstractWith few curative treatments for kidney diseases, increasing attention has been paid to regenerative medicine as a new therapeutic option. Recent progress in kidney regeneration using human-induced pluripotent stem cells (hiPSCs) is noteworthy. Based on the knowledge of kidney development, the directed differentiation of hiPSCs into two embryonic kidney progenitors, nephron progenitor cells (NPCs) and ureteric bud (UB), has been established, enabling the generation of nephron and collecting duct organoids. Furthermore, human kidney tissues can be generated from these hiPSC-derived progenitors, in which NPC-derived glomeruli and renal tubules and UB-derived collecting ducts are interconnected. The induced kidney tissues are further vascularized when transplanted into immunodeficient mice. In addition to the kidney reconstruction for use in transplantation, it has been demonstrated that cell therapy using hiPSC-derived NPCs ameliorates acute kidney injury (AKI) in mice. Disease modeling and drug discovery research using disease-specific hiPSCs has also been vigorously conducted for intractable kidney disorders, such as autosomal dominant polycystic kidney disease (ADPKD). In an attempt to address the complications associated with kidney diseases, hiPSC-derived erythropoietin (EPO)-producing cells were successfully generated to discover drugs and develop cell therapy for renal anemia. This review summarizes the current status and future perspectives of developmental biology of kidney and iPSC technology-based regenerative medicine for kidney diseases.