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.
Dr. Harald C. Ott, senior author of a paper describing the research that was published online
Sunday by the journal Nature Medicine, said that 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.
Dr. 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
network of proteins that retains the structure of the blood vessels and
other components of the organ. In addition to rat kidneys, Dr. 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.
Dr. 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.
Dr. 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.
As for scaling the technique up to work for people, Dr. Ott said one
approach would be to use decellularized pig kidneys, which are 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.”
SOURCE : http://www.nytimes.com/2013/04/15/science/rat-kidneys-made-in-lab-seen-as-step-to-human-transplants.html
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