June 28, 2022

Complex kidney tissue generated entirely from mouse embryonic stem cells for improved kidney research and, eventually, artificial kidney transplantation

Kidney disease, commonly known as chronic kidney disease or CKD, kills more people than breast or prostate cancer combined (NVS 2021 report of 2018 data). It is an underestimated public health emergency. Kidney disease affects one in every three adults in the US (about 80 million people). Women (14%) are more likely than males to have kidney disease (12%). A total of 37 million Americans is projected to be affected. The risk of CKD is much higher for Americans with diabetes or high blood pressure, the two most frequent causes of kidney disease. Kidney disease affects about one-third of diabetics and one-fifth of those with high blood pressure. Heart disease and a family history of kidney failure are two more risk factors for kidney disease.

Despite the fact that kidney illness is common in the US, up to 9 out of 10 persons with the condition are unaware of it. Early-stage kidney disease normally has no symptoms, and many people living with it are not even aware of having it until it is too late. The renal disease generally worsens over time, leading to kidney failure as well as other health issues including stroke or heart attack. End-stage kidney disease (ESKD) is a kind of kidney failure that can be treated with a kidney transplant or dialysis. It affects around 2 out of every 1,000 people in the US.

Key Kidney Disease Statistics

Chronic kidney disease (CKD) – CKD is most common among people with ages above 65 years

End-stage kidney disease (ESKD) – Nearly 786,000 people in the US are living with ESKD

In recent research, scientists used mouse embryonic stem cells to generate sophisticated kidney tissue. These organoids have the potential to pave the path for improved kidney research and, eventually, artificial kidneys for human transplant.

A team of researchers from Kumamoto University (Japan) generated sophisticated 3D kidney tissues in the lab using just cultured mouse embryonic stem (ES) cells. These organoids have the potential to pave the path for improved kidney research and, eventually, artificial kidneys for human transplant. Dr. Ryuichi Nishinakamura and his team were able to generate the last piece of a three-part puzzle that they had been working on for several years by focusing on an often-overlooked tissue type of organoid generation in their research, a type of organ tissue made up of various support and connective tissues called the stroma. Organs are made up of parenchyma and stroma, with the latter coordinating the formation of organotypic structures. Despite recent breakthroughs in organoid technology, the generation of organ-specific stroma and the recapitulation of complicated organ shapes from pluripotent stem cells (PSCs) remain difficult. This research constructs an in vitro induction strategy for stromal progenitors (SPs) from mice PSCs by revealing the in vivo molecular characteristics of the renal stromal lineage at a single-cell resolution level. When induced SPs are combined with two differentiating parenchymal progenitors (nephron progenitors and ureteric buds), the completely PSC-derived organoids replicate the complex kidney structure, with multiple types of stromal cells seen along developing nephrons and branching ureteric buds. Thus, incorporating PSC-derived lineage-specific stroma into parenchymal organoids would open the way for organotypic architecture and functions to be recapitulated.

The kidney is an essential organ for maintaining good health because it filters waste and excess water from the blood. It is a complicated organ that is formed by the interaction of three elements. Various research groups, including Dr. Nishinakamura’s team at Kumamoto University’s Institute of Molecular Embryology and Genetics (IMEG), have already developed protocols to produce two of the components (the nephron progenitor and the ureteric bud) from mouse ES cells. The IMEG team has established a way to create the third and final component, kidney-specific stromal progenitor, in mice in their most recent study. Furthermore, the researchers were able to create a kidney-like 3D tissue in vitro by merging these three components, which included highly branching tubules and various other kidney-specific features.

This is the first time the researchers have reported on the in-lab creation of such a complicated kidney structure from scratch, according to the researchers. The first two components have previously been induced in human iPS cells by the IMEG team. A similarly complicated human kidney should be possible if this last component can also be made from human cells. When the three sections were put together, the final structure was discovered to have a kidney-like design. The researchers anticipate that their work will be utilized to progress kidney research and may potentially lead to the development of a transplantable organ in the future. Researchers are presently working extremely hard to develop a completely functional human kidney. In the long run, they intend to utilize their discoveries to evaluate medications for a variety of disorders, as well as for transplantation.

Reference

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

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