Induced Pluripotent Stem Cells as Kidney Disease Therapy

Researchers here investigate the transplant of induced pluripotent stem cells-derived progenitor cells produced from the recipient's tissues as a possible way to spur regeneration of kidney damage, such as the fibrosis characteristic of chronic kidney disease. Like many forms of stem cell therapy, this appears to produce benefits due to the signal molecules generated by the transplanted cells. That in turn suggests that near future therapies emerging from stem cell research will largely involve providing the signals directly, not via cells, in ever more sophisticated efforts to control the behavior of native cells. This present phase of cell transplant development will be used to gain the knowledge needed to build therapies lacking cells but which have the same beneficial effects.

One promising way to treat diseased or damaged kidneys is cell therapies that include the transplantation of renal progenitor cells, which can then develop into the cells needed for full recovery. Acquiring a sufficient number of progenitor cells has been difficult, however, which is why scientists have considered induced pluripotent stem cells (iPSCs), since they can be expanded at significantly high levels and then differentiated into the progenitors.

Researchers transplanted iPSC-derived renal progenitors into the kidney subcapsule, which is at the kidney surface of a mouse model with acute kidney injury. Even though the transplanted cells never integrated with the host, mice that received this transplant showed better recovery, including less necrosis and fibrosis, compared with mice that received transplants of other cell types. One reason attributed to this improvement was the use of cells that expressed Osr1 and Six2. Although these two factors are known markers of renal progenitors, until now researchers had not exclusively used cells that expressed both for cell therapies.

Another conclusion from the study was that because the cells did not integrate into the kidney, their therapeutic effects were the result of paracrine actions that included the secretion of key renoprotective factors. While most stem cell therapies aim for integration, these findings could have important clinical implications. Foremost is that it is one of the first to show the benefits of using human iPS cell-derived renal lineage cells for cell therapy. Second, fibrosis is a marker of progression to chronic kidney disease, suggesting that the paracrine effects could act as preventative therapy for other serious ailments. Finally, these effects could give 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."

Link: http://www.eurekalert.org/pub_releases/2015-07/cfic-isp072115.php

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