One of the ultimate quests in the stem cell field – growing organs to repair diseased or damaged ones – took a significant step forward this week. In a first, researchers at the University of Manchester, in the U.K., showed that human embryonic stem cell-derived kidney tissue forms into functional kidney structures, capable of filtering blood and producing urine, when implanted under the skin of mice.
When a person has end-stage kidney disease, their body can no longer filter out waste products and extra fluid from the blood which leads to serious health complications, even death. Blood filtration therapy, called dialysis, can substitute for a kidney but the average life expectancy is only about 10 years for patients receiving dialysis. Kidney transplants are another answer for treating kidney disease, but organ availability is in limited supply. About 2.2 million people die worldwide from a lack of access to these treatment options. So other therapeutic approaches to help end-stage kidney disease sufferers are sorely needed.
The current study, published in Stem Cell Reports, used human embryonic stem cells to grow kidney tissue in the lab. While the lab-grown tissues showed hallmarks of kidney structures, they were unable to fully develop into mature kidney structures in a culture dish. So the scientists tried implanting the human kidney tissue under the skin of mice and left it there for 12 weeks. The team showed that kidney structures, called glomeruli, which play a key role in filtering the blood, formed over that time and had become vascularized, or connected with the animal’s blood supply. The team further showed those structures were functional by injecting a fluorescently tagged substance called dextran. Tracing the fate of the dextran in the blood showed that it had been filtered and taken up by tubular structures in the kidney tissue which indicates urine production had begun.
Professor Sue Kimber, one of the leaders of the study, summed up the significance and current limitations of these results in a press release:
“We have proved beyond any doubt these structures function as kidney cells by filtering blood and producing urine – though we can’t yet say what percentage of function exists. What is particularly exciting is that the structures are made of human cells which developed an excellent capillary blood supply, becoming linked to the vasculature of the mouse.
Though this structure was formed from several hundred glomeruli, and humans have about a million in their kidneys – this is clearly a major advance. It constitutes a proof of principle- but much work is yet to be done.”
To be sure, curing a person suffering from end-stage kidney disease with a stem cell-grown kidney is some ways off. But, on the nearer horizon, this advance will provide a means to study the human kidney in a living animal, a powerful tool for uncovering insights into kidney disease and new therapeutic approaches.