Stem cell hope for genetic kidney disease

A team of US scientists has managed to successfully treat mice with symptoms of a genetic kidney disease, using bone marrow stem cells. The researchers, based at the Beth Israel Deaconess Medical Center, transplanted stem cells into animals affected by Alport syndrome, and saw a significant improvement in their condition. It appears that the stem cells have managed to regenerate the damaged tissue and restore some of the lost kidney function, say the scientists, who published their findings in the Proceedings of the National Academy of Sciences.

Alport syndrome causes the kidneys' waste filtration system to break down. Affected individuals are born with a faulty version of one of three collagen genes, which together make the main protein component of the glomerular basement membrane (GMB). The GMB normally acts as a sieve, filtering waste products out of the blood. But in people with Alport syndrome, this membrane doesn't work properly, so blood and protein are lost in the urine, while some urea waste is retained in the body. There is currently no cure for the condition, apart from a kidney transplant or lifelong dialysis.

Previous studies have shown that stem cells derived from bone marrow have the ability to regenerate some types of damaged tissue, although it is still unclear exactly how this happens. In the latest study, the researchers decided to see if such cell transplants might help repair some of the damage caused by Alport syndrome. They gave bone marrow transplants to mice born with a type IV collagen gene mutation, using a fluorescent tag to identify the transplanted cells.

Thirteen weeks later, they found that ten per cent of the cells in the animals' kidneys were fluorescing, and that their symptoms were greatly improved. Treated mice had 70-80 per cent less protein in their urine, and 86 per cent less urea in their blood than untreated mice. 'This is encouraging, as it means that you do not need to transform a significant number of kidney cells to see an improvement', team leader Raghu Kalluri told ScienceNOW news.

The scientists say they aren't sure whether the transplanted cells are turning into new kidney cells, or whether they are simply fusing with existing unhealthy cells and passing on their genetic information. It is a key issue to resolve if the approach is ever to be used therapeutically, according to expert Richard Poulson of Cancer Research UK. This is because if the transplanted cells are exchanging genetic material with existing cells, then crucial genes could be inappropriately switched on or off, he explained.