Bohong Guo, J K Zhang, Xuening Fang, Yanjie Liu, Yueyang Deng, Yuxin Xue, Z L Wang, Xiaotao Dong, Mengqi Jia, X Li
Chronic kidney disease (CKD) has emerged as a critical public health challenge worldwide, and organ donor shortages underscore the urgent need for alternative therapeutic strategies. Advances in stem cell technologies have enabled the generation of kidney organoids, providing innovative platforms to model renal development, investigate disease mechanisms, support drug discovery, and explore applications in regenerative medicine. Yet, limitations such as immature tissue architecture, insufficient vascularisation, and unaddressed safety concerns still hinder their translation into regenerative medicine. In this review, we summarise the fundamentals of kidney development, current differentiation approaches, and the signalling and epigenetic mechanisms underlying organoid lineage specification. We further highlight the roles of bioengineering innovations and single-cell transcriptomics in establishing evaluation frameworks and enhancing structural complexity. We finally emphasise that existing optimisation frameworks, primarily focused on improving differentiation efficiency and enforcing relatively restricted lineage specification, may prove inadequate for bridging the gap to clinical translation. Instead, the most promising paradigm shift involves the convergence of bioengineering modulation and high-resolution functional assessment to facilitate the synchronised advancement of organoid complexity and physiological utility.