Wake Forest Institute for Regenerative Medicine
Scientists use a mesh material as a scaffold to seed bladder cells as they grow. After three to six weeks, the cells are transplanted inside the child's urethra, where they eventually replace the damaged tissue.
Scientists have been trying for years to grow replacement parts for defective or damaged organs. Now, a report published in a medical journal tells a success story about fixing the urinary tracts of five young Mexican boys. The procedure could ultimately help thousands of children.
For going on 30 years, scientists have been trying to grow replacement parts for diseased, defective or damaged tissues and organs. They've had more disappointments than successes. But now and again, they come up with results that rekindle the flame.
The latest involves five Mexican boys between 10 and 14 who suffered terrible damage to their urinary tracts from auto accidents. They were unable to urinate normally.
"When they first came in, they had a leg bag that drains urine, and they have to carry this bag everywhere they go," says Dr. Anthony Atala of Wake Forest University in North Carolina. "It's uncomfortable and painful. So these children were mostly sitting or bed-bound."
Atala and his colleagues, including doctors at Metropolitan Autonomous University in Mexico City, figured out a way to grow a new urethra, the tube that empties urine from the bladder, for the children.
The first thing they did was remove a small patch of each boy's bladder.
"The piece of tissue we take is very small -– less than half the size of a postage stamp," Atala says. The tissue contains two types of cells –- muscle cells and endothelial cells, which form the lining of the urethra and other hollow tubes in the body, such as blood vessels.
The researchers multiplied these cells in the lab until there were 100 million of them. Then they used the cells to "seed" a cylinder made out of biodegradable material. A week or so later, the cells covered the cylinder, creating a tube of tissue about as long as a deck of cards, with a diameter a little bigger than a soda straw.
The researchers stitched these made-to-order tissue tubes into the gaps in the boys' urinary systems. Eventually, the biodegradable "scaffolding" melts away.
That was as long as six years ago. Today, in every case, the boys' re-engineered urinary tracts are functioning normally, the researchers say.
The unusually long follow-up is perhaps the most important aspect of the new report, which appears online in the British journal The Lancet.
"Typically, if you're going to see these structures fail, they can fail early or they can fail late," Atala says. "But if you have them with this long of a follow-up, then you know they're going to do well over time."
Atala says the tissue grafts have grown along with the boys, who have had major growth spurts since their urinary repairs. "So the body is recognizing the implant as its own," Atala says.
He says the procedure has transformed the boys' lives. "These children are now totally normal," he says. "They're running around and doing the things they usually do."
The procedure might ultimately help thousands of children — not only those who suffer injury, but those with urinary birth defects, which afflict about one in every 150 male births.
But it won't happen tomorrow. First the trick has to be replicated in many more cases.
"We are only talking about five patients, which is certainly not enough for widespread, meaningful conclusions," says Dr. Dario Fauzo of Children's Hospital in Boston, a researcher not connected with Atala's research.
Fauzo welcomed the new results but says he'd like more evidence that the implanted cells actually stuck around. Alternatively, they might have somehow stimulated other cells in the boys' systems to heal the damage. Either way, he says, it appears they "did something helpful," but it would be important to know how they did it.
Atala says animal studies have shown that existing cells can't grow more than a half-centimeter into the kind of biodegradable "scaffolding" like the ones implanted in the Mexican children. So he thinks the implanted cells must have persisted.
In 2009, Atala's Wake Forest group implanted tissue-engineered bladders in nine patients, seven of whom were followed long-term. He says all seven of those replacement bladders are still functioning normally.
Other researchers have reported success in growing windpipes and blood vessels — though no one has yet grown a solid organ, such as a liver or kidney.
But, in another sign that the field of tissue engineering may be entering a new phase, Fauzo is set to try correcting some birth defects diagnosed by ultrasound in gestating fetuses. If the experiment wins Food and Drug Administration approval, he plans to harvest fetal cells from the amniotic fluid, multiply them in the laboratory, and direct them into becoming tissues that can replace a defective windpipe or repair a hernia in the fetus's diaphragm.
If it works, the replacement part would be ready by the time the baby is born. Beyond that, Fauzo hopes it will be possible to use the lab-grown tissues to repair birth defects before birth.
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