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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. We modified the culture protocol and maintained kidney organoids in medium containing FGF9 for 1 additional week compared to the control protocol (Takasato). In comparison to the control, the FGF9-treated kidney organoids had reduced cartilage at day 7 + 25 and diminished chondrocyte marker expression. Importantly, the renal structures assessed by immunofluorescence were unaffected by the FGF9 treatment. This reduction of cartilage produces a higher quality kidney organoid that can be maintained longer in culture to improve their maturation for further in vivo work.
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http://dx.doi.org/10.1038/s41536-025-00428-9 | 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.
View Article and Find Full Text PDF