Stem cell and bioengineering approaches for end-stage renal disease: a comprehensive review

End-stage renal disease (ESRD) is a major global health burden, and current treatments, such as dialysis and kidney transplantation, remain constrained by donor shortages, procedure-related complications, and reduced long-term quality of life. Regenerative medicine, particularly stem cell-based approaches, offers promising next-generation strategies for kidney repair and replacement. This review summarizes the current understanding of kidney development and intrinsic regenerative capacity and evaluates the therapeutic potential of hematopoietic stem cells, mesenchymal stem cells (MSCs), kidney-derived stem cells, and induced pluripotent stem cell (iPSC)-derived kidney organoids. Evidence from preclinical models demonstrates renoprotective and immunomodulatory effects across multiple stem cell types, whereas early-phase clinical trials have reported favorable safety profiles and preliminary signals of the efficacy of MSC-based therapies. iPSC- and organoid-based approaches present additional challenges, including incomplete vascularization, immature nephron structures, risks of tumorigenicity, immune compatibility issues, and the need for reproducible good manufacturing practice (GMP)-compliant manufacturing. Advances in biomaterials, organoid engineering, and vascularization strategies may help overcome these barriers. Overall, stem cell-based regenerative therapies show substantial potential to complement or ultimately reduce the reliance on dialysis and transplantation. Continued technological innovations and rigorously designed clinical trials are critical to translate these promising approaches into clinical practice.