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Updated: Sep 9, 2025
Author Spotlight: Optimizing iPSC Differentiation for Efficient Production to Generate Kidney Organoids
Published on: September 1, 2023
FGF9 treatment reduces off-target chondrocytes from iPSC-derived kidney organoids
Virginie Joris1, Anika Schumacher1, Maria Paula Marks1
1Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
Abstract:
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.
Insights
Adding FGF9 to kidney organoid cultures reduces unwanted cartilage formation. This improvement enhances kidney organoid quality and maturation for future research into drug toxicity and kidney diseases.
Area of Science:
- Stem Cell Biology
- Regenerative Medicine
- Nephrology
Background:
- Drug nephrotoxicity and kidney diseases are significant clinical concerns.
- In vitro kidney models are crucial for studying drug toxicity and disease mechanisms.
- Induced pluripotent stem cell-derived kidney organoids show promise but require optimization for extended culture and improved purity.
Purpose of the Study:
- To modify existing kidney organoid culture protocols to enhance their quality and suitability for long-term studies.
- To investigate the effect of fibroblast growth factor 9 (FGF9) on reducing non-renal cell populations, specifically cartilage, in kidney organoids.
Main Methods:
- Kidney organoids were cultured using a modified protocol involving the addition of FGF9 to the culture medium for an extended period (1 week) compared to the standard Takasato protocol.
- Chondrocyte marker expression and cartilage presence were assessed in FGF9-treated and control organoids.
- Renal structure integrity was evaluated using immunofluorescence.
Main Results:
- FGF9 treatment significantly reduced cartilage formation in kidney organoids by day 7+25.
- Expression of chondrocyte markers was diminished in FGF9-treated organoids.
- Key renal structures within the organoids remained unaffected by the FGF9 treatment.
Conclusions:
- Supplementation with FGF9 improves kidney organoid quality by reducing cartilage contamination.
- This enhanced quality allows for longer maintenance and improved maturation of kidney organoids.
- Optimized kidney organoids are more suitable for in vivo applications and advancing research in nephrotoxicity and kidney disease modeling.
