Kidney disease can condemn patients to a lifetime of dialysis, with a transplant the only possibility for relief. Now researchers have shown that bone marrow stem cells might one day provide a better alternative. Mice given a bone marrow transplant containing these cells experienced a dramatic reduction in the symptoms associated with Alport syndrome--a genetic disease in which the kidneys' filtration system breaks down.
The kidneys filter waste from the blood with a dense network of capillaries called the glomerulus. High blood pressure in this region forces unwanted molecules through the sievelike glomerular basement membrane (GBM) and its associated cells. The waste drips into the renal tubule, from which it is eventually excreted as urine, while the purified blood returns to the veins.
But in Alport syndrome, this filter often fails. Patients have a mutation in the genes that encode its main component--a threadlike, fibrous protein called type IV collagen. Proper pore formation doesn't occur, so protein and blood leak into the urine. And because the cells that aid filtering don't interact with the GBM properly, not all waste products are removed from the blood.
Harvard biologist Raghu Kalluri and colleagues wondered if help could come from bone marrow stem cells, which have been shown to transform into other body tissues (ScienceNOW, 19 November 2003). The team gave mice with a type IV collagen gene mutation a bone marrow transplant where all the cells, including the stem cells, were tagged with a fluorescent marker. Thirteen weeks later, 10% of the cells in the unhealthy kidneys were glowing, including podocytes (which are thought to produce type IV collagen) and mesangial cells (which support the structure of the GBM).
Kalluri is unsure whether this means that the bone marrow cells had actually become new podocytes or mesangial cells, or whether the new cells had just fused with the old ones or transferred their nuclei. Either way, the effect was dramatic given the small percentage of glowing cells: Mice infused with bone marrow stem cells had 70% to 80% less protein in their urine and 86% less toxic urea in their blood than did controls.
"This is encouraging, as it means that you do not need to transform a significant number of kidney cells to see an improvement," says Kalluri, whose team publishes its results online this week in Proceedings of the National Academy of Sciences. How the stem cells reach their destination remains a mystery. The team thinks that the cells in damaged kidneys attract the stem cells with a chemical lure that is not present in healthy kidneys.
Researchers still need to nail down exactly how the new therapy works, says histopathologist Richard Poulsom of Cancer Research UK's London Research Institute, to avoid side effects. If the transplanted cells are exchanging genetic material with the original cells, for example, essential genes could be shut off or potentially harmful ones could be turned on.
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