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A member of Dr Atala's
team places cells on a biodegradable bladder scaffold
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The world's first working internal
organs grown outside the body have been successfully
transplanted into humans. Last week, researchers revealed
that lab-grown bladders have been functioning in six
teenagers and children with spina bifida — a neural
tube birth defect that causes incontinence and kidney
failure — for up to five years. The breakthrough
comes from the Institute of Regenerative Medicine in
Winston-Salem, North Carolina. The institute's star
player is the prolific Dr Tony Atala, who presides over
a lab that could be mistaken for a renovated Frankenstein's
castle. But when it comes to growing human organs, he's
your man.
"We have about 80 people working
on many different tissue types," said Dr Atala. "There
are tubularized structures such as blood vessels; other
hollow structures like the uterus; solid organs such
as the kidney, liver, pancreas and heart. Basically,
even though we're dealing with many different tissues,
the technique is remarkably similar." The process was
described in the Lancet on April 4.
AN
ORGAN IN THE MAKING
Dr Atala has previously grown and implanted urethras
in humans, but he said bladders represent a whole new
challenge. Just getting the cells to grow in vitro
took over a decade's research. The breakthrough came
when researchers cut a bladder with a laser in unrelated
research, only to find it completely healed 24 hours
later. The team was able to identify the cells that
were doing the repair work — and they would later
become the seeds of regenerated bladders. "They're not
undifferentiated stem cells," Dr Atala explained, "but
progenitor cells specific to the bladder. They're already
committed to that lineage."
The bladder is composed of two
different cellular layers, with a layer of collagen
sandwiched in between. Dr Atala's team separated the
two cell types and grew them both, then seeded them
onto a scaffold of collagen. In later versions, the
scaffold was made of composite materials. "[The scaffold]
degrades over time and the body replaces it with its
own collagen layer. So you end up with standard three-layer
tissue," he explained. Once in the body, new blood vessels
and nerve cells vascularize and innervate the new organ.
The result in patients with spina
bifida — who have elevated pressure within the
bladder — is remarkable, but not perfect. "We found
that patients' pressures were lowered, which improved
kidney function. It also improved their dryness and
their continence period," said Dr Atala. "These patients
had improved quality of life."
BLADDER,
ANYONE?
Spina bifida patients aren't the only ones who stand
to benefit from this breakthrough. "About 35 million
patients in the US suffer from bladder problems and
while not all of them would be candidates, many would,"
Dr Atala said. Bladder exstrophy, for example, is a
condition in which a baby's bladder forms outside the
body. Then there are traumatic accidents, and older
patients may face problems with bladder cancer, he said.
"The risk of growing bladders from malignant cells can
be avoided. You can find cells from other parts of the
urinary tract that have the same properties with less
propensity for cancer. You'd be able to take the cells
from the ureter, for example, or the renal pelvis,"
he explained.
Dr Atala's optimistic his lab-grown
bladders will replace the standard treatment, which
involves grafting tissue from the gastrointestinal tract.
"Growing a bladder costs about $4000 per engineered
construct. In terms of cost to benefit, when looking
at the alternative, you have to consider patients' subsequent
problems."
Intestinal tissue has been used
to repair bladders for over a hundred years. But it's
hardly an ideal solution. "The intestine is designed
to absorb, whereas the bladder is designed to excrete
waste," explained Dr Atala. "So you can imagine the
problems. Your body starts absorbing all these things
that you need to get rid of, and you end up with metabolic
abnormalities, electrolyte disturbances, stone formation,
bone resorption, increased urinary tract infections,
increased mucus production and ultimately increased
malignancy."
Dr Atala fully intends to put his
optimism to the test. "At the end of this year we're
going to add a new series of patients to increase the
numbers, and next year we're going to expand the indications.
We're going to go to adult patients with neurogenic
bladders, whether from spinal cord injury or other conditions,
and then we're going to expand that to bladder cancer."
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