Scientists Grow World’s First Engineered Urethra, Created From Patients’ Cells

By Patrick Morgan | March 8, 2011 12:42 pm

In a society where pill-popping is the answer to many a medical malady, severely dysfunctional or damaged organs are especially frustrating—they’re usually beyond the reach of any known drugs. Cell-based therapy, though, is no drug: Using patients’ own cells, medical experts have successfully grafted the first engineered-from-scratch urethras.

The story starts with five Mexican boys, aged 10 to 14, whose urethras were damaged beyond repair because of accidents.

“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.” [NPR]

Currently the usual treatment calls for an artificial graft, which has a failure chance as high as 50% (and failure here means a lifetime of infections and incontinence). “When an organ or tissue is irreparably damaged or traumatically destroyed, no amount of drugs or mechanical devices will restore the patient back to normal,” regenerative medicine expert Chris Mason, from University College London, told the BBC.As outlined in their Lancet study, Atala and his colleagues at Wake Forest Institute for Regenerative Medicine didn’t use conventional methods to repair these five urethras: They enlisted the help of the patients’ own cells to heal them by first harvesting, as Atala told NPR, a patch of cells “less than half the size of a postage stamp” from the boys’ bladders. Specifically, they took muscle cells and endothelial cells, which compose the lining of our body’s many tubes, including urethras.

After isolating the cells they’d need to create the necessary tissues, they then multiplied the cells in culture for several weeks until they had roughly 100 million of them—just enough to get the job done. And using the same material used for dissolvable stitches, they created a tiny drinking-straw-shaped mesh, and carefully added muscle cells to the outside part of the tube and lining cells to the inside part.

Dr Anthony Atala … described the process as “very much like baking a layer cake”. [The Guardian]

The cells were allowed to incubate for another week to ensure they were secured to the mesh, before the experts grafted the tissue-engineered urethra into gaps in their urinary tracks.

Six years on the grafts are still doing well, looking and functioning exactly like a normal urethra in the five boys who are now entering their teens. “It’s like they now just have their own urethras,” Atala told The Guardian. [The Guardian]

But how can the scientists be so sure of the successful after a mere six years? Part of the answer lies in the fact that the grafts have actually grown as the boys—who are now teenagers—have grown, indicating that their bodies have recognized the grafts (minus the mesh scaffolding, which has since disintegrated) as their own.

“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.” [NPR]

This urethra engineering is the latest success in cell-based therapies. In 2009, the same team grafted tissue-engineered bladders into nine patients, and other groups have made windpipes from a patient’s stem cells, and even a replacement jaw. Even though nobody has grown whole solid organs yet, like livers or kidneys, Atala’s team hopes to use this treatment on other tubular structures in the body, like blood vessels, and to start work on over 30 other tissue and organ replacements. In Australia, researchers at Bond University are currently working to grow a functional eye, tissue engineering expert Patrick Warnke told The Guardian.

At the moment, though, Atala and his colleagues are celebrating the success of the world’s first tissue-engineered urethra. With one out of 150 male babies suffering from urinary birth defects, this procedure could be a valuable new tool in modern medicine. But since this success is only based on a handful of patients, it’s going to take quite a few more replications before this becomes commonplace.

Related Content:
Discoblog: Need a New Pancreas? It May Come From a Sheep
Science Not Fiction: We Can Rebuild You: 8 Ways Science Can Fix Your (or Your Cat’s) Broken Body
80beats: Making Pig Stem Cells Raises the Possibility of Animal Organ Donors
DISCOVER: Tissue Engineering

Image: Wake Forest Institute for Regenerative Medicine

CATEGORIZED UNDER: Health & Medicine, Living World
  • http://www.genomed.com David Moskowitz MD FACP

    The author of this blog is clearly not a biochemist. Life depends on molecules, and a drug has already proven to be far superior to efforts at tissue engineering.

    There’s a big difference between a urethra, which has only one or two cell types, and an entire kidney, which has hundreds, put together in the most intricate way, which we still don’t understand. It’s roughly the difference between your driveway and your house: building one doesn’t mean you have a clue how to build the other. It’s fair to say that we won’t be printing kidneys any time soon.

    On the other hand, my paper showing how to prevent 90% of kidney failure just by popping the right dose of the right pill was published in 2002. If it had gotten the slightest media attention, there would be no waiting list now for cadaver kidneys; there’d be more than enough kidneys for the relatively few kidney patients who still needed them. No living donors would be necessary. And money wouldn’t be wasted on trying to print kidneys.

    Indeed, 450,000 American dialysis patients wouldn’t have died unnecessarily, the equivalent of 9 Vietnam Wars, and $225 billion could have been saved from unnecessary dialysis. The tragic waste of taxpayers’ lives and money continues. With silly stories like this one, one gets the feeling the waste may be deliberate.

    My paper, and the three confirmatory papers that appeared after 2002, are referenced in http://www.genomed.com/images/guyot_dec09nl.pdf, along with a surprising list of who’s dropped the ball public health-wise (hint: everybody).

    My company, GenoMed (www.genomed.com), nevertheless intends to make the world dialysis-free by 2020. Anybody with diabetes or high blood pressure should contact us before they lose more than half their kidney function. Above a serum creatinine of 2 mg/dl, we can’t help them, any more than Dr Atala and his printer will ever be able to. As we Baby Boomers first learned how to say in the 1960s, it’s time to get real.

  • terry

    Fantastic.
    I suffered circumcision under the Ontario College of Physicians and Surgeons directive to circumcise every boy born in Ontario starting around 1946. I suffered like any rape victim would with flash backs and fear, eventually complaining to and then abandoning my mother. By 1997 I was restoring but here it is 2011 and I am still in trouble physically and mentally. I see hope finally in fixing something that was not broken. How about it Ontario politicians ?
    terry

  • Sam

    Wow, David… That’s a pretty biased opinion you have there. I guess it’s not surprising you throw a plug in there glorifying your own research (and your company!). Let’s not kid ourselves, though; it’s no Nature paper. If you are so thoroughly convinced that your drug is THE method for reversing kidney disease, then you have shared in the proverbial ball dropping. I’m also not sure from where you derive your opinion that, “…a drug has already proven to be far superior to efforts at tissue engineering.” Tissue engineering is in its infancy, whereas drug therapeutics date back to before history was being kept.
    It’s disheartening to witness someone with your credentials poo-poo these types of findings. You also cherry-pick your example, citing the kidney, an organ with which you obviously have much expertise. How about the liver, though? It consists primarily of two cell types. Could one not recapitulate these types of results toward hepatic application? How about cardiac muscle? Neurons? I think you know the answer to those questions.
    Also, if you know anything about mesoderm progenitor cells, then you would know one cell is capable of forming many different cell types, and once committed to this lineage the frequency of teratoma formation is extremely low (even in unsorted cells). This is like taking the ingredients that can be combined to build your house AND your driveway, and squashing them into one component: it can become anything you please with the proper instructions. Therefore, Dr., your argument is flawed. The author of your post (you) are clearly not a stem cell biologist or a scientist.
    I do agree that your approach toward the kidney may be a viable option, but stem cell and iPS cell-based therapy are the future, like it or not. If you fail to recognize this then you may again “drop the ball public health-wise”.

  • http://discoverytimes.blogspot.com/ Discovery Blog

    I am not a science guy like you people. But whatever info I could get from this post is really exciting and interesting. Grafting an engineered-from-scratch urethras by using the patients’ own cells has opened up a new horizon in medical science… I think

  • Sam

    Discovery Blog,

    You are correct! That’s my point, but more succinct. And, yes, it has opened a new horizon in medical science. These types of things have been done in mice and rats, but it is very encouraging to see success in humans. Thank you for the article.

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