Researchers from the Massachusetts General Hospital in the US have grown rat kidneys in the laboratory that produced urine when transplanted into living animals. This is an important step towards the production of customised organs for transplantation into people with kidney failure, which could replace donor organ transplants.
Patients with kidney failure can be treated with dialysis, but can only be cured with a kidney transplant. About 8,000 people are waiting for a donor kidney in Germany, but only 3,000 kidney transplants take place each year. Patients may wait up to seven years for a donor kidney and many lose their lives during that time.
A few research groups have attempted to make artificial kidneys, and some are trying to genetically modify pigs so their kidneys can be used in human transplants, but Harald Ott and his team take a different approach: they hope to grow kidneys in the laboratory using the patient's own cells. This would put an end to donor organ shortage and immune rejection problems. "If this works, there wouldn't be any need for immunosuppression or dialysis anymore, it would be a revolution," says Raymond Vanholder, a nephrologist at the Ghent University Hospital in Belgium and president of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA). After a transplant patients need to take immunosuppressant drugs throughout their entire lives. And despite these treatments, which can have severe side-affects, many organ recipients will have an acute rejection or lose kidney function within 10 years.
A recipe to make kidneys
In a new Nature Medicine study, Ott and colleagues describe how they successfully 'bioengineered' and transplanted rat kidneys into living animals. They started by taking kidneys from dead rats and stripping them of cells using a detergent commonly used in household cleaning products. This leaves an intact kidney-shaped protein scaffold, complete with all the complex microscopic vascular and tubular kidney structures.
Next the researchers coated the kidney 'skeletons' with new cells by pushing them through the kidney main artery and the ureter (a tube that takes urine to the bladder). In these rat kidney prototypes, they used kidney cells from a newborn rat and human umbilical cord cells to make blood vessels. Getting the cells to stick to the kidney scaffolds was the trickiest step (if too much pressure was applied the scaffolds exploded), but after a few days in an incubator the cells rearranged into three-dimensional tissues that looked like kidney structures under the microscope. The different rat kidney cell types seemed to be at the right place. This was very promising, and indeed, after 12 days, when blood was passed through the kidneys they started producing urine. Further tests showed that these bioengineered kidneys partially restored most kidney functions, like filtering the blood and producing urine.
Could these kidneys work in living animals? When the team transplanted the regenerated kidneys into living rats that had one of their kidneys removed, the new kidneys immediately filled with the rats' blood, without clot formation or bleeding, and produced urine.
Customised organs on demand
Bioengineered kidneys made 'on demand' with the patient's own cells would make organ waiting lists and immune rejections a thing of the past, and this would completely change the lives of patients with kidney failure. But unfortunately this scenario is still a long way down the line. Vanholder says "I think this is very beautiful research [...] but it has to be confirmed independently by other studies, and before it can be used in the human clinical situation it will take many years."
Many challenges remain ahead. In Ott's rat regenerated kidneys, a small percentage of kidney cells attached to the wrong place in the kidney scaffold, and the kidneys functioned poorly when compared to normal kidneys. Ott believes this is due to the immaturity of the cells implanted on the scaffold, and that using other cell types and letting them mature for longer may improve kidney function. Another challenge will be to scale up the cell coating method to larger organs like human kidneys. The team has already succeeded in making pig and human kidney scaffolds, but coating them with new cells is a more complicated step.
Ott's group previously used these techniques to make hearts and lungs, and other groups are currently trying to develop livers in similar ways. So could this technology replace donor organ transplants in the future? Vanholder answers "It's unlikely that this research will emanate in a real application very soon [...] but if it works it will be a fantastic thing, it may solve a lot of problems, like the need for dialysis and the shortage of donor organs for transplant."