Scientists make rat kidneys in laboratory

Achievement could lead to the ability to create replacement organs for people with kidney disease

A functional lab-made kidney. Photograph: Reuters

A functional lab-made kidney. Photograph: Reuters

Mon, Apr 15, 2013, 08:40

Researchers at Massachusetts General Hospital in Boston have made functioning rat kidneys in the laboratory, a bioengineering achievement that may one day lead to the ability to create replacement organs for people with kidney disease.

The scientists said the rat kidneys produced urine in the laboratory as well as when transplanted into rats. The kidneys were made by stripping donor kidneys of their cells and putting new cells that regenerate tissue into them.

Stripping an organ leaves a natural scaffold of collagen and other compounds, called the extracellular matrix, which provides a framework for new cells and preserves the intricate internal architecture of the kidney as well as its basic shape.

Harald C. Ott, senior author of a paper describing the research that was published online Sunday by the journal Nature Medicine, said the work was still in its early stages and that there were many hurdles to creating fully functional kidneys for people.

But he noted that replacement organs made in this way would have advantages over those made with artificial scaffolds or other techniques.

"The huge benefit would be that it's fully implantable in the shape of a kidney," he said. About 17,000 people with end-stage kidney disease receive a donor organ each year in the United States, but more than five times as many patients are on waiting lists.

In 2011, nearly 5,000 people died while awaiting transplants. Bioengineered kidneys, especially if made using nonhuman sources, could ease or eliminate this organ shortage.

Dr Stephen F. Badylak, a researcher at the University of Pittsburgh and a pioneer in the use of extracellular matrix in regenerative medicine, said that similar work had been done with hearts and other organs.

"The real value of this study is that it's the kidney and it's a proof of concept, and the clinical need is so great," said Dr Badylak, who was not involved in the research. Ott developed the technology of stripping organs of their cells, called decellularization, while at the University of Minnesota. The process uses a detergent to wash away the living tissue, leaving a glistening network of proteins that retains the complex structure of the blood vessels and other components of the organ.

In addition to rat kidneys, Mr Ott's group decellularized pig and human kidneys. To make the regenerated rat kidneys, human cells were "seeded" into the blood vessel portions of the organ, and kidney cells from newborn rats were used for the other parts. The kidneys were then put into an incubating chamber for up to five days, allowing the tissues to grow.

One problem with using decellularized tissue, Dr Badylak said, is that often when the regenerated organ is reconnected to a blood supply, clotting occurs after a short time, effectively ending the experiment. Ott said his team saw no signs of bleeding or clotting, although the transplant experiments were ended after a short time, before the kidneys stopped functioning.

Mr Ott said that while the bioengineered kidneys produced rudimentary urine, they did not function as well as natural ones. One reason for this, he said, may be the relative immaturity of the kidney cells used. His group is now working on identifying the kinds of cells to be used to repopulate the organ.

"It's not ideal yet, or complete yet," he said. As for scaling the technique up to work for people, he said one approach would be to use decellularized pig kidneys, which are similar in size to human ones and readily available, and seed them with human cells. When a patient needed a new kidney, "You'd take a kidney matrix off the shelf," he said. "Then in an ideal world you'd take cells from that patient and create a kidney on demand."

The New York Times