Researchers have created implantable bioengineered kidneys made of living cells that have allowed rats to clean their blood and generate urine.
Their ultimate goal is to make new organs for patients suffering from kidney disease by using their own cells.
Kidneys filter wastes and liquids from the blood, and disorders afflicting them can be fatal. The most severe form of chronic kidney disease plagues nearly 1 million patients in the United States, and while blood dialysis machines can help them survive, the only cure is a kidney transplant.
Roughly 18,000 such transplants take place annually in the U.S. Yet about 100,000 Americans with advanced kidney disease are currently waiting for a donor organ, and there is a 5 percent to 10 percent mortality rate for those on the waiting list. Even those lucky enough to receive a donor’s kidney have to take drugs their entire lives to suppress their immune system so it doesn’t reject the transplant, which poses many health risks and cannot totally eliminate the possibility of eventual organ rejection. Indeed, 20 percent of recipients experience an episode of rejection within five years of transplantation, and about 40 percent of recipients will die or have their grafts fail within 10 years after transplantation.
All these problems have led scientists to attempt to create replacement kidneys. Instead of building machines, surgeon Harald Ott at Harvard Medical School and Massachusetts General Hospital in Boston and his colleagues want to develop living kidneys made from the patient’s own cells.
Building bespoke kidneys
The researchers started with cherry-sized kidneys from dead rats and used detergent solutions to strip all the cells from them. What remained were the scaffolds of material the cells were normally embedded in that maintained the original architecture of the organs, a strategy previously used to create bioengineered hearts, lungs and livers.
The scientists next seeded the scaffolds with kidney and blood vessel cells from the recipient rats. The cells and the scaffolds were then placed into bioreactors, machines that supplied liquids filled with nutrients, oxygen and other compounds that helped the cells grow and fill their scaffolds within 12 days.
Ott and his colleagues transplanted these bioengineered kidneys into living rats that each had one kidney removed. The fact these implants kept the complex architecture of their scaffolds meant they could be connected to the recipients’ blood and urinary systems.
The investigators discovered the implants could produce urine, with no evidence of bleeding or clot formation. They detailed their findings online April 14 in the journal Nature Medicine.
More work to do
They caution that their bioengineered organs showed dramatically reduced function compared with healthy kidneys. "Once transplanted, they had somewhere about 5 to 10 percent of the function of normal kidneys," Ott says. "The cells we had were still immature."
Still, current blood dialysis machines are only providing 10 percent to 15 percent of the functioning of healthy kidneys. “If we can get to 20 percent, that’s not great, but not far off from helping a lot of people,” Ott says.
The researchers now hope to scale up to human-sized kidneys, which are roughly 100 times bigger than rat kidneys. So far, they have shown the cell-removal technique they applied on rat kidneys also works on pig and human kidneys — they are now investigating ways of growing all the cell types needed in human kidneys and refining their cell-seeding and bioreactor techniques to handle human-sized organs.
"We’ve shown an initial proof of concept that has some promise," Ott says. "Now it’s time to start the nitty-gritty work, to solve all the technical problems."
The jury is still out as to which approach is best to engineering an organ, Ott cautions. “For instance, other scientists are also trying to make kidneys using 3-D printers,” he says.
Top Image: This is a previously decellularized rat kidney after reseeding with endothelial cells, to repopulate the organ’s vascular system, and neonatal kidney cells. Courtesy Massachusetts General Hospital Center for Regenerative Medicine.