Potential use of iPS cells to combat acute kidney disease …

Posted: August 2, 2015 at 8:47 pm

Whilst transplantation often remains the only effective treatment for acute kidney disease, a new study from Kyoto University points to a future where renal progenitor cells derived from iPSCs could be transplanted into affected kidneys to combat these debilitating conditions.

In recent years, a popular avenue of investigation for treating kidney disease and damage has been transplantation of renal progenitor cells (RPCs), which can develop into the variety of cells required for organ repair. One problem with this line of study has been growing the number of RPCs required for effective treatment. This investigation, lead by Professor Kenji Osafune and published in Stem Cells Translational Medicine, shows iPSCs can be expanded and differentiated into RPCs at high enough levels to make them a strong candidate for the therapy.

One issue outstanding with this potential therapy is the difficulty associated with transplanting the RPCs directly into kidney parenchyma, with few studies managing to introduce sufficient cell numbers. The kidney is a very solid organ, which makes it very difficult to bring enough number of cells upon transplantation, Osafune explained.

To circumvent this problem, the team transplanted RPCs derived from iPSCs into the kidney subcapsule at the kidney surface. These cells never integrated into the host organ, but the mice receiving the treatment showed better recovery from their acute kidney injury nevertheless. Compared to control experiments, introduction of RPCs was concomitant with reduced necrosis and fibrosis of the damaged kidneys. Osafune has suggested that these improvements may be due to the RPCs expressing two known renal progenitor marker proteins, Osr1 and Six2, which have not been tested together until now.

As the cells did not integrate into the host kidney, another mode of action must have caused the benefits observed. The study concluded that paracrine secretions of renal protective factors from the RPCs caused the improvements seen in the treated mice. As kidney fibrosis marks progression towards chronic disease, Osafune hinted the paracrine secretions could be utilised as a preventative therapy for other diseases, or 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.

Sources: Toyohara T, Mae SU, Sueta SU et al. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury In Mice. Stem Cells Translational Medicine. doi: 10.5966/sctm.2014-0219

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