Scientists bioengineer functional, transplantable rat kidneys
About 100,000 people in the United States alone are on the list to receive a kidney transplant and 400,000 are kept alive by kidney dialysis machines. Unfortunately, there are only 18,000 kidneys available each year in the U.S. and those lucky enough to receive one face a lifetime of immunosuppressant drugs. To increase the supply and remove the risk of tissue rejection, a team of researchers led by Harald Ott of the Massachusetts General Hospital Center for Regenerative Medicine has built an experimental bioengineered kidney that not only produces urine, but has been successfully transplanted into a rat.
The bioengineered kidney is based on a technique developed by Ott while working as a research fellow at the University of Minnesota. The team started with the kidney of a newborn rat and stripped the living cells from the organ using detergents. This left a collagen scaffold that was repopulated with human endothelial cells to replace the lining of the vascular system and kidney cells from the newborn rat.
The kidney was then placed in a bioreactor for up to twelve days. To ensure that the right cells get to the right part of the kidney, vascular cells were seeded through the renal artery and kidney cells through the ureter. Meanwhile, a pressure gradient was set up between the kidney scaffold and the solution it was suspended in to disperse the cells throughout the whole organ. The last step required particular care because too great a pressure would have caused the kidney to explode.
Collagen scaffolding, ready for repopulation with new kidney and vascular cells (Image: Ott Laboratory, Massachusetts General Hospital Center for Regenerative Medicine)
After the kidney was finished, it was tested by passing blood through the vascular system and draining off the urine that it produced, showing that the kidney was working. The kidney was then transplanted into a rat where it replaced one of the original kidneys. It produced urine as soon as the blood supply was restored and showed no bleeding or clot formation. The bioengineered kidney couldn't match the natural kidney in performance, but the team says that this was due to the cells’ immaturity.
"Further refinement of the cell types used for seeding and additional maturation in culture may allow us to achieve a more functional organ," said Ott. "Based on this initial proof of principle, we hope that bioengineered kidneys will someday be able to fully replace kidney function just as donor kidneys do. In an ideal world, such grafts could be produced 'on demand" from a patient's own cells, helping us overcome both the organ shortage and the need for chronic immunosuppression. We're now investigating methods of deriving the necessary cell types from patient-derived cells and refining the cell-seeding and organ culture methods to handle human-sized organs."
The technique used to make the kidney was previously employed in experiments aimed at constructing bioengineered hearts, lungs and livers. The team believes that it could work on a larger scale by stripping cells from pig and human kidneys that would otherwise be unsuitable for transplantation and replacing their cells with healthier, more compatible ones grown from the patient’s stem cells.
"What is unique about this approach is that the native organ's architecture is preserved, so that the resulting graft can be transplanted just like a donor kidney and connected to the recipient's vascular and urinary systems," said Ott. "If this technology can be scaled to human-sized grafts, patients suffering from renal failure who are currently waiting for donor kidneys or who are not transplant candidates could theoretically receive new organs derived from their own cells."
The team’s results were published in Nature Medicine.
This video from Nature takes a closer look at the breakthrough.
Source: Massachusetts General Hospital