Vascularization and maturation of kidney organoids: a comprehensive review of technological trends and challenges

Chronic kidney disease is a global health issue, and novel therapeutic alternatives to dialysis and kidney transplantation must be developed. Human-induced pluripotent stem cell-derived kidney organoids recapitulate developmental processes and mimic kidney-like structures in vitro and have thus attracted attention for treating chronic kidney disease. However, the limited vascularization and immaturity of human-induced pluripotent stem cell-derived kidney organoids remain major barriers to their clinical application. The latest technological advances and specific challenges in kidney organoid vascularization and maturation were thoroughly examined in this review. Diverse approaches were considered, including coculturing with endothelial cells, in vivo transplantation, applying biomaterials and microfluidic systems, controlling molecular signaling, and metabolic reprogramming. However, issues persist such as low reproducibility, lack of standardization, insufficient functional evaluations, and inadequate safety assessments. Future studies should focus on developing multifactorial and strategies for integrating multiple cell types, establishing maturation assessment criteria, and verifying the long-term functionality and safety of three-dimensional bioprinting technologies. Technologies for the vascularization and maturation of kidney organoids show promise as foundational methods for use innovative regenerative medicine and the development of drug discovery therapies.