Induced Pluripotent Stem Cell-Derived Kidney Progenitor Cells Heal Kidneys in Laboratory Animals


The kidney is a crucial organ for human survival and human flourishing. This organ filters metabolic wastes from the blood and if the kidney does not work, the body slowly poisons itself.

When the kidneys fail to work properly, they must be replaced by transplantation of a tissue-matched kidney from a donor. However, if the kidney is not completely damaged, then it might be possible to heal it by means of cell therapies. For example, if we could transplant renal progenitor cells into the kidney that then differentiate into kidney-specific tissues, then we could potentially replace damaged tissues in the kidney and help the kidney fully recover. The tough part of such a treatment strategy has been acquiring a sufficient number of kidney progenitor cells. However, scientists have considered using induced pluripotent stem cells (iPSCs), since these cells can be expanded in culture to very high numbers of cells that can be effectively differentiated into kidney progenitors.

Induced pluripotent stem cells are made from mature, adult cells by means of a combination of genetic engineering and cell culture techniques. These cells have the potency to differentiate into any cell type in the human body. Ideally, renal progenitors could be transplanted directly into the kidney parenchyma, but, again, this is not a simple-to-solve problem. “The kidney is a very solid organ, which makes it very difficult to bring enough number of cells upon transplantation,” explains Professor Kenji Osafune. Dr. Osafune’s laboratory is at the Center for iPS Cell Research and Application (CiRA) at Kyoto University, Japan, and is using iPSCs to investigate new treatments for kidney disease. Several studies have successfully transplanted adequate numbers of kidney progenitors to treat kidney disease.

In a new study, Dr. Osafune has collaborated with Astellas Pharma Inc., in order to potentially design a solution that can solve the problem of treating the kidney with exogenous cells. In this study, Osafune and his colleagues tried a different way to deliver the kidney progenitor cells. Instead of injecting cells directly into the kidney, they transplanted their iPSC-derived renal progenitors into the kidney subcapsule that is at the kidney surface.

Kidney Capsule

The mice that received the cells were suffering from acute kidney injury. Even though the transplanted cells never integrated with the host, mice that received this transplant showed better recovery, including less cell death (necrosis) and scarring (fibrosis) compared with mice that received transplants of other cell types.

Damaged kidney tissue (left) of an AKI model mouse shows high levels of fibrosis (blue). Treatment with Osr1+Six2+ cell therapy significantly ameliorates the fibrosis (right) of another AKI model mouse.
Damaged kidney tissue (left) of an AKI model mouse shows high levels of fibrosis (blue). Treatment with Osr1+Six2+ cell therapy significantly ameliorates the fibrosis (right) of another AKI model mouse.

Osafune attributed the improvement in his laboratory mice to the use of cells that expressed the Osr1 and Six2 genes. The Osr1 and Six2 proteins are known markers of renal progenitor cells, but until this particular study, researchers had not exclusively used cells that expressed both of these proteins for cell therapies.

Kidney Progenitor cells

Another conclusion from the study was that because the cells did not integrate into the kidney, their therapeutic effects were the result of secreted proteins that promoted kidney healing and protection. While most stem cell therapies aim for integration of the transplanted cells, the results of these experiments could have important clinical implications. In particular, this experiment is one of the first to show the benefits of using human iPS cell-derived renal lineage cells for cell therapy. Secondly, scarring of the kidney is a marker that indicated progression of the kidney to chronic kidney disease. Since scarring was significantly reduced in these experiments, these data suggest that the paracrine effects of the transplanted cells could act as preventative therapy for other serious ailments. Finally, Osafune believes these effects could provide valuable clues for drug discovery. “There is no medication for acute kidney injury. If we can identify the paracrine factor, maybe it will lead to a drug.”

From:  Takafumi Toyohara, et al., “Cell therapy using human induced pluripotent stem cell-derived renal progenitors ameliorates acute kidney injury in mice” Stem Cells Translational Medicine.

Australian Researchers Make A Kidney in the Laboratory With Stem Cells


Stem cell researchers from the University of Queensland in Australia have successfully grown a kidney in the laboratory with stem cells. This new breakthrough will almost certainly open the door to improved treatments for patients with kidney disease, and bodes well for the future of organ bioengineering.

Mini-kidney in dish. (Source: University of Queensland)
Mini-kidney in dish. (Source: University of Queensland)

The principal investigator of this research project, Professor Melissa Little, from University of Queensland’s Institute for Molecular Bioscience (IMB), said that new treatments for kidney disease were urgently needed.

“One in three Australians is at risk of developing chronic kidney disease and the only therapies currently available are kidney transplant and dialysis,” Little said. “Only one in four patients will receive a donated organ, and dialysis is an ongoing and restrictive treatment regime. We need to improve outcomes for patients with this debilitating condition, which costs Australia $1.8 billion a year.”

Little’s research team designed a new step-wise protocol to coax embryonic stem cells to gradually form all the required kidney-specific cell types and to induce them to “self-organize” into a mini-kidney in a dish.  The embryonic stem cell line HES3 was used in this work, which derived by Reubinoff and others in the laboratory of Alan Trounson in 2000.

“During self-organization, different types of cells arrange themselves with respect to each other to create the complex structures that exist within an organ, in this case, the kidney,” Little said. “The fact that such stem cell populations can undergo self-organization in the laboratory bodes well for the future of tissue bioengineering to replace damaged and diseased organs and tissues. It may also act as a powerful tool to identify drug candidates that may be harmful to the kidney before these reach clinical trial.”

Despite the success of this research, Little cautioned that she and other kidney researchers had a great deal of work to do to before this protocol might be ready for human trials. Regardless, it is a very exciting step forward.

The Queensland Minister for Science and Innovation Ian Walker congratulated Little and her co-workers for their advances, and added that biomedical research was crucial in ensuring a healthier future for Queenslanders.

“The work by the IMB research team is an important milestone in developing improved treatments for chronic kidney disease and will ensure those with the condition can continue to live fulfilling and productive lives,” Walker said.

Little’s research team included Dr. Minoru Takasato, Pei Er, Melissa Becroft, Dr. Jessica Vanslambrouck, from IMB, and her collaorators, Professors Andrew Elefanty and Ed Stanley, from the Murdoch Children’s Research Institute and Monash University.

The research is published in the scientific journal Nature Cell Biology and supported by the Queensland Government, the Australian Research Council, as part of the Stem Cells Australia Strategic Research Initiative, and the National Health and Medical Research Council of Australia.