3D mouse kidney organoid generated in lab using iPSC-derived renal stroma

Researchers from Kumamoto University (Japan) have created a 3D mouse kidney organoid using cultured embryonic stem cells from mice. The findings may lead to the development of artificial kidneys for human transplants.

The researchers previously induced two of the necessary components – the nephron progenitor and the ureteric bud – from the embryonic stem cells of mice. The findings have been published in Nature Communications.

The team established a method to induce the final component needed to create the organoid – a kidney specific stromal progenitor – in mice. By merging these components in vitro, the researchers produced a kidney-like 3D tissue comprised of specific renal structures.

Additionally, the research team successfully induced the first two components needed for the organoid from iPSCs. The research team suggest a similarly complex human kidney may be achievable if able to execute the same with a third component.

However, the team expressed that there are still difficulties when it comes to generating a functional kidney, partly due to the structure of kidney organoids in mice. For instance, the kidney organoids found in mice lack an elongated ureter and are unconnected to the host urinary outlet, meaning a urinary flow route is not established.

Researchers were unable to suggest whether the stromal progenitor induction process will be appropriate for human iPSCs. For some human kidney structures to be developed, the quality of the induced nephrotic progenitors and ureteric buds need to be modified based on information gathered in vivo.

It was demonstrated that the development program of renal stromal progenitors is possible and that the cells can be successfully induced in vitro. The researchers expressed that the study provides a proof-of-concept for the generation of organoids derived purely from iPSCs. It also serves as a useful platform to study heterogeneous stromal cells in organs.

Ryuichi Nishinakamura (Kumamoto University), one of the study’s authors, stated “we are now working very hard to generate a fully functional human kidney. We hope to use our developments to screen drugs for various diseases, and for transplantation in the long run.” These organoids may lead to superior kidney research and might even aid in the development of artificial kidneys for human organ recipients.

Sources: https://www.nature.com/articles/s41467-022-28226-7#Sec11

Tanigawa S, Tanaka E, Miike K et al. Generation of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma. Nature Communications. 13(1), 611 (2022).