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.

Human Umbilical Cord Mesenchymal Stem Cells Form Prostate Gland Tissues


Repairing the prostate gland is an important goal in regenerative medicine. However, finding the right cell for the job has proven to be a slow and tedious search.

To that end, Wei-Qiang Gao and his colleagues from Shanghai Jiao Tong University in Shanghai, China, used mesenchymal stem cells from human umbilical cord (hUC-MSCs) to test the ability of these cells to differentiate into prostate-specific cells. They combined hUC-MSCs with rat urogenital sinus stromal cells (rUGSSs) and then transplanted these cells into the renal capsule of BLB/c nude mice for two months. Cells tend to grow very well under the kidney capsule because this particular microenvironment has a very rich blood supply. Also the rUGSSs provide soluble, secreted factors that induce the hUC-MSCs to differentiate into prostate-specific cells.

After removing the implanted tissue, analyses of the implanted cells showed that the hUC-MSCs differentiated into prostate epithelial-like cells. This was confirmed by the presence of prostate specific antigen on the surfaces of these hUC-MSCs. Prostate specific antigen is only found on prostate cells, which is the reason why this protein is such a good indicator of prostate cancer. Also, the hUC-MSCs formed prostatic glandular structures that had the same cellular architecture as a normal prostate (see figure F below). Additionally, the human origin of the hUC-MSCs was further confirmed by the detection of a protein called human nuclear antigen, which is specific to human cells.

Human UC-MSCs combined with rUGSSs can generate prostate glands. Mice were sacrificed 2 months after co-transplantation surgery, and the kidneys from the cell implanted nude mice were collected. (A) Graft initiated with hUC-MSCs alone and (B) rUGSSs alone were used as negative control, respectively. (C) Graft derived with hUC-MSCs and rUGSSs. (D–F) Histological analyses of the sections of the graft stained for haematoxylin and eosin (H&E). (D) Note that while hUC-MSCs alone and (E) rUGSSs single cell type transplantation fail to regenerate prostate glandular structures. (F) co-transplantation of hUC-MSCs and rUGSSs gives rise to prostate glandular structures. Scale bar 50 mm.
Human UC-MSCs combined with rUGSSs can generate prostate glands. Mice were sacrificed 2 months after co-transplantation surgery, and the kidneys from the cell implanted nude mice were collected. (A) Graft initiated with hUC-MSCs alone and (B) rUGSSs alone were used as negative control, respectively. (C) Graft derived with hUC-MSCs and rUGSSs. (D–F) Histological analyses of the sections of the graft stained for haematoxylin and eosin (H&E). (D) Note that while hUC-MSCs alone and (E) rUGSSs single cell type transplantation fail to regenerate prostate glandular structures. (F) co-transplantation of hUC-MSCs and rUGSSs gives rise to prostate glandular structures. Scale bar 50 mm.

This interesting paper shows that hUC-MSCs can differentiate into epithelial-like cells that are normally derived from embryonic endodermal tissue. This implies that MSCs from umbilical cord can be used to repair not only prostate glands, but also other endodermally-derived tissues.