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Updated: Jan 8, 2026
Author Spotlight: Optimizing iPSC Differentiation for Efficient Production to Generate Kidney Organoids
Published on: September 1, 2023
Modeling kidney fibrosis and tubular regeneration in iPSC-derived kidney organoids
Shengbing Li1, Quincy Nlandu2,3, Thierry P P van den Bosch4
1Department of Internal Medicine, Erasmus MC, Erasmus MC Transplant Institute, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Background:
Kidney fibrosis is one of the pathological hallmarks of chronic kidney disease, likely contributing to the loss of kidney function. The mechanisms leading to kidney fibrosis and its reversibility is only partially understood, which hampers the development of therapeutic targets. Therefore, it is crucial to establish a robust human in vitro model that can be used to study kidney fibrosis and potential regeneration.
Methods:
Human induced pluripotent stem cells (iPSC) were differentiated into kidney organoids. Fibrotic injury was induced by mimicking hypoxia (1% O2 48 h), inflammation (interleukin-1 beta (IL-1β) 96 h) or a combination (hypoxia and IL-1β). Organoids were harvested at injury onset and up to 2 weeks post-injury. Fibrosis was assessed by mRNA and protein expression of fibronectin (FN1) and collagen type I, regeneration was evaluated through the presence of CD133+ and CD24+ progenitor cells and markers for differentiated kidney cell types.
Results:
The combination of hypoxia and IL-1β induced the strongest fibrotic response with significant upregulation of FN1 and collagen type I, and loss of tubular and glomerular markers. Over time, FN1 levels realigned with the control group, whereas collagen type I remained elevated. Tubular markers (Villin and ECAD) recovered to near-control levels, coinciding with increased CD133+ and CD24+ cell population and Ki67 expression. In contrast, PODXL+ glomerular structures showed limited recovery.
Conclusions:
We present a reproducible human kidney organoid model that captures both fibrotic remodeling and tubular regeneration following clinically relevant injury. This platform offers a valuable tool for studying kidney-specific fibrosis dynamics and testing anti-fibrotic or pro-regenerative strategies.
Insights
This study developed a human kidney organoid model to investigate kidney fibrosis and regeneration. The model shows fibrotic injury can be followed by tubular regeneration, offering a tool for testing new therapies.
Area of Science:
- Nephrology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Kidney fibrosis is a key factor in chronic kidney disease progression.
- Understanding fibrosis mechanisms and reversibility is crucial for therapeutic development.
- A robust human in vitro model is needed to study kidney fibrosis and regeneration.
Purpose of the Study:
- To establish a human in vitro model using kidney organoids to study fibrosis and regeneration.
- To investigate the dynamics of fibrotic remodeling and tubular recovery after injury.
- To provide a platform for testing anti-fibrotic and pro-regenerative strategies.
Main Methods:
- Human induced pluripotent stem cells (iPSC) were differentiated into kidney organoids.
- Fibrotic injury was induced using hypoxia and/or interleukin-1 beta (IL-1β).
- Fibrosis and regeneration markers (e.g., FN1, collagen I, CD133, CD24) were assessed post-injury.
Main Results:
- Combined hypoxia and IL-1β induced significant fibrotic response (FN1, collagen I upregulation).
- Tubular markers recovered, accompanied by increased progenitor cells (CD133+, CD24+) and proliferation (Ki67).
- Glomerular structures (PODXL+) showed limited recovery, while collagen I remained elevated.
Conclusions:
- A reproducible human kidney organoid model effectively mimics fibrotic remodeling and tubular regeneration.
- This model is valuable for studying kidney fibrosis dynamics and evaluating therapeutic interventions.
- The platform supports research into anti-fibrotic and pro-regenerative treatments for kidney disease.
