Medical breakthrough: test-tube kidney works in rats
15 April 2013
In a medical breakthrough, a fully laboratory-grown kidney has been successfully transplanted into rats, where they were filtering and discharging urine like a natural kidney, US scientists say.
Similar techniques to make simple body parts have already been used in humans, but the kidney is one of the most complicated organs produced by such technology.
The successful experiment, the results of which were published in the journal Nature Medicine, shows that the engineered kidneys are so far less effective than natural ones.
It nonetheless increases the potential for human-scale versions, which could provide an inexhaustible supply of kidneys, eliminating the need for recipients to wait for (or in India, buy!) a matching donor kidney.
Similar techniques have already been applied successfully in people with simpler tissue, such as windpipes. But the kidney is by far the most complex organ successfully recreated.
"If this technology can be scaled to human-size grafts, patients suffering from renal failure, who are currently waiting for donor kidneys, could theoretically receive an organ grown on demand," says Harald Ott, head of the team that developed the rat kidneys at the Massachusetts General Hospital in Boston.
"In an ideal world, such grafts could be produced from patient-derived cells, enabling us to overcome both donor organ shortages and the need for long-term immunosuppression drugs."
Currently in the US alone, 18,000 transplants are carried out each year, but 100,000 Americans remain on waiting lists.
Such lists would of course be much longer in more heavily-populated countries, particularly in Asia.
To make the rat kidneys, Ott and his colleagues took kidneys from healthy "donor" rats and used a chemical solution to wash away the native cells, leaving behind the organ's scaffold. Because this is made of collagen, a biologically inert material, there is no issue of the recipient's body rejecting it.
Next, the team set about re-growing the "flesh" of the organ by coating the inner surfaces of the scaffold with new cells. In the case of humans, these would likely come from the recipient, so all the flesh would be their own.
The kidney was too complex to use the approach applied to the windpipe – in which its scaffold was coated by simply immersing it in a bath of the recipient's cells.
In their new approach, the team placed the kidney scaffolds in glass chambers containing oxygen and nutrients, and attached tubes to the protruding ends of the renal artery, vein and the ureter – through which urine normally exits the kidney.
They recoated the insides of the blood vessels by flowing human stem cells through the tubes attached to the artery and vein. Through the ureter, they fed kidney cells from newborn rats, re-coating the labyrinthine tubules and ducts that make up the kidney's urine filtration system.
It took many attempts to establish the precise pressures at which to feed the cells into the organ, as if it was growing in an embryonic rat. Remarkably, given the complexity of the kidney, the cells differentiated into exactly those required in the different compartments of the organ. "We found the correct cell types homed in to specific regions in the organ matrix," says Ott.
The kidneys, which took about a fortnight to fully recoat, worked both in the lab and when transplanted into rats. They filtered out and discharged urine, although they did not sieve it as well as a natural kidney would. Ott is confident that the function can be improved by refining the technique.
The team is now attempting the same procedure using human kidneys, and also pig kidneys, which could be used to make 'scaffolds' if there were a scarcity of human donors. The team has already successfully repopulated pig kidneys with human cells, but Ott says further studies are vital to guarantee that the pig components of the organ do not cause rejection when transplanted into humans.
The fact that heart valves and other "inert" tissues from pigs are already successfully used in humans without rejection suggests that this will not be a big problem.