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Updated: Dec 24, 2025

Optimization of Renal Organoid and Organotypic Culture for Vascularization, Extended Development, and Improved Microscopy Imaging
Published on: March 28, 2020
Cellular and Molecular Mechanisms of Kidney Development: From the Embryo to the Kidney Organoid
Niloofar Khoshdel Rad1,2, Nasser Aghdami3, Reza Moghadasali1
1Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Abstract:
Development of the metanephric kidney is strongly dependent on complex signaling pathways and cell-cell communication between at least four major progenitor cell populations (ureteric bud, nephron, stromal, and endothelial progenitors) in the nephrogenic zone. In recent years, the improvement of human-PSC-derived kidney organoids has opened new avenues of research on kidney development, physiology, and diseases. Moreover, the kidney organoids provide a three-dimensional (3D) in vitro model for the study of cell-cell and cell-matrix interactions in the developing kidney. In vitro re-creation of a higher-order and vascularized kidney with all of its complexity is a challenging issue; however, some progress has been made in the past decade. This review focuses on major signaling pathways and transcription factors that have been identified which coordinate cell fate determination required for kidney development. We discuss how an extensive knowledge of these complex biological mechanisms translated into the dish, thus allowed the establishment of 3D human-PSC-derived kidney organoids.
Insights
Human kidney organoids derived from induced pluripotent stem cells (iPSCs) offer a powerful 3D model for studying kidney development and disease. This research reviews key signaling pathways and transcription factors crucial for kidney organoid development.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Kidney development relies on intricate signaling and cell communication among four progenitor populations.
- Human induced pluripotent stem cell (hiPSC)-derived kidney organoids are advancing research into kidney development, physiology, and disease.
- These 3D organoids serve as valuable in vitro models for studying cell-cell and cell-matrix interactions in renal development.
Purpose of the Study:
- To review critical signaling pathways and transcription factors governing kidney development.
- To explore how understanding these mechanisms enables the creation of 3D hiPSC-derived kidney organoids.
- To highlight the potential of kidney organoids for studying renal development and disease.
Main Methods:
- Review of existing literature on kidney development signaling pathways.
- Analysis of transcription factors involved in cell fate determination during kidney development.
- Discussion of the translation of developmental biology knowledge into the generation of kidney organoids.
Main Results:
- Identification of key signaling pathways (e.g., Wnt, FGF, BMP) and transcription factors (e.g., SIX2, WT1) essential for kidney development.
- Demonstration that knowledge of these pathways facilitates the directed differentiation of hiPSCs into kidney organoids.
- Progress in creating more complex and vascularized kidney organoids in vitro.
Conclusions:
- Understanding the molecular mechanisms of kidney development is crucial for generating functional kidney organoids.
- hiPSC-derived kidney organoids represent a significant advancement for in vitro modeling of kidney development and disease.
- Further research into vascularization and higher-order complexity is needed for more complete kidney organoid models.
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