Regenerative potential of induced pluripotent stem cells derived from patients undergoing haemodialysis in kidney regeneration.
Susumu TajiriShuichiro YamanakaToshinari FujimotoKei MatsumotoAtsuhiro TaguchiRyuichi NishinakamuraHirotaka James OkanoTakashi YokooPublished in: Scientific reports (2018)
Kidney regeneration from pluripotent stem cells is receiving a lot of attention because limited treatments are currently available for chronic kidney disease (CKD). It has been shown that uremic state in CKD is toxic to somatic stem/progenitor cells, such as endothelial progenitor and mesenchymal stem cells, affecting their differentiation and angiogenic potential. Recent studies reported that specific abnormalities caused by the non-inherited disease are often retained in induced pluripotent stem cell (iPSC)-derived products obtained from patients. Thus, it is indispensable to first assess whether iPSCs derived from patients with CKD due to non-inherited disease (CKD-iPSCs) have the ability to generate kidneys. In this study, we generated iPSCs from patients undergoing haemodialysis due to diabetes nephropathy and glomerulonephritis (HD-iPSCs) as representatives of CKD-iPSCs or from healthy controls (HC-iPSCs). HD-iPSCs differentiated into nephron progenitor cells (NPCs) with similar efficiency to HC-iPSCs. Additionally, HD-iPSC-derived NPCs expressed comparable levels of NPC markers and differentiated into vascularised glomeruli upon transplantation into mice, as HC-iPSC-derived NPCs. Our results indicate the potential of HD-iPSCs as a feasible cell source for kidney regeneration. This is the first study paving the way for CKD patient-stem cell-derived kidney regeneration, emphasising the potential of CKD-iPSCs.
Keyphrases
- induced pluripotent stem cells
- chronic kidney disease
- end stage renal disease
- stem cells
- patients undergoing
- mesenchymal stem cells
- cell therapy
- cardiovascular disease
- type diabetes
- peritoneal dialysis
- human health
- single cell
- ejection fraction
- bone marrow
- endothelial cells
- case report
- gene expression
- skeletal muscle
- newly diagnosed
- drug induced
- climate change
- stress induced
- insulin resistance
- wound healing