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A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures that resemble the native kidney organ. These miniature kidney-like structures can also be derived from primary patient cells and thus provide simplified context to observe how mutations in kidney-disease-associated genes affect organogenesis and physiological function. In the past several years, advances in kidney organoid technologies have achieved the formation of renal organoids with enhanced numbers of specialized cell types, less heterogeneity, and more architectural complexity. Microfluidic bioreactor culture devices, single-cell transcriptomics, and bioinformatic analyses have accelerated the development of more sophisticated renal organoids and tailored them to become increasingly amenable to high-throughput experimentation. However, many significant challenges remain in realizing the use of kidney organoids for renal replacement therapies. This review presents an overview of the renal organoid field and selected highlights of recent cutting-edge kidney organoid research with a focus on embryonic development, modeling renal disease, and personalized drug screening.
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http://dx.doi.org/10.3390/cells12040549 | DOI Listing |
Clin Kidney J
September 2025
Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
Genome editing technologies, particularly clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, have transformed biomedical research by enabling precise genetic modifications. Due to its efficiency, cost-effectiveness and versatility, CRISPR has been widely applied across various stages of research, from fundamental biological investigations in preclinical models to potential therapeutic interventions. In nephrology, CRISPR represents a groundbreaking tool for elucidating the molecular mechanisms underlying kidney diseases and developing innovative therapeutic approaches.
View Article and Find Full Text PDFAdv Healthc Mater
September 2025
Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
Kidney organoids are powerful tools for renal disease modeling and nephrotoxicity screening, yet their limited structural complexity-particularly the underdevelopment of ureteric bud (UB) lineages-remains a major limitation. A novel differentiation protocol is developed that short-term activation of retinoic acid (RA) signaling during the early intermediate mesoderm (IM) stage, enabling co-induction of anterior and posterior IM lineages. This eliminates the need for UB co-culture and supports the formation of kidney organoids containing complete nephron segments.
View Article and Find Full Text PDFCell Mol Life Sci
September 2025
Transplantation Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
The aim of this study is to establish an in vitro co-culture system to model allograft rejection using kidney organoids system derived from human induced pluripotent stem cells (hiPSCs). We co-cultured kidney organoids derived from wild-type hiPSCs with HLA-mismatched peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) for 24 h. To assess allogeneic rejection modeling, we measured the expression of HLA molecules, (HLA-ABC and HLA-DR), and evaluated cellular damage in the kidney organoids.
View Article and Find Full Text PDFNat Commun
August 2025
Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at University of Southern California, Los Angeles, CA, USA.
The kidney maintains fluid homeostasis by reabsorbing essential compounds and excreting waste. Proximal tubule cells, crucial for reabsorbing sugars, ions, and amino acids, are highly susceptible to injury, often leading to pathologies necessitating dialysis or transplants. Human pluripotent stem cell-derived kidney organoids offer a platform to model renal development, function, and disease, but proximal nephron differentiation and maturation in these structures is incomplete.
View Article and Find Full Text PDFNPJ Regen Med
August 2025
Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
Renal failure due to drug nephrotoxicity or disease is frequently observed in patients. The development of in vitro models able to recapitulate kidney biology offers new possibilities to study drug toxicity or model diseases. Induced pluripotent stem cell-derived kidney organoids already show promise, but several drawbacks must be overcome to maintain them in culture, among which is the presence of non-renal cell populations such as cartilage.
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