FGF9 treatment reduces off-target chondrocytes from iPSC-derived kidney organoids

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 one 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. HighlightsO_LIKidney organoids develop cartilage between days 7+18 and 7+25 C_LIO_LIExtending the FGF9 supplementation reduces cartilage and chondrocyte markers C_LIO_LIFGF9-treated organoids present less EMT marker expression than control organoids C_LIO_LIRenal structures are not affected by the extended FGF9 treatment C_LI eTOC blurbLaPointe and colleagues showed that a one-week extension of FGF9 supplementation in iPSC-derived kidney organoids leads to a reduction of off-target cartilage. The renal structures are not impacted by FGF9 treatment and EMT markers are reduced. This modified organoid protocol will enable longer culture periods, a benefit for the use of organoids for screening or therapies.