The next step is to try to recreate the entire organ from scratch. The technique could make it possible to reconstruct the penises of men who have suffered injuries or those of children born with genital abnormalities. "If you have a child born with ambiguous genitalia, it's a life-changing event," says Anthony Atala of Harvard Medical School, whose team carried out the work.
It could also provide an alternative to the crude methods currently used to enlarge the organ, such as injecting fat cells or cutting the penis's suspensory ligament and "pulling out" more of the internal part. Instead, a patient would have penile cells removed by a doctor and, a few weeks later, the organ or parts of it grown using the cells could be surgically implanted.
While the particular nature of the research is likely to attract much attention, it's also one of the most impressive attempts at tissue and organ engineering to date. "The penis is more complex than any of the organs we have engineered so far," says Atala, whose team has already created fully functional bladders that may soon be implanted in people.
The penis is more difficult to recreate because it has more functions and, unlike the bladder, is also a solid organ. It consists of three main cylinders, encased in an outer layer of connective tissue, skin, blood vessels and nerves (see Graphic). The two biggest cylinders, made of spongy material that swells during an erection, are the corpora cavernosa. The third tube encases the urethra. Of those structures, the corpus cavernosum is the most challenging to replace or reconstruct. It contains specialised muscle and endothelial cells- the cells that line blood vessels- and its structure is hard to mimic. Yet this is the part that Atala has been able to grow.
His team first extracted three-dimensional scaffolds of collagen from the erectile tissue of rabbits. They also took samples of the specialised muscle and endothelial cells from penises of each of the rabbits destined to receive the implants. These cells were grown separately at first, and then added to the collagen matrix in the appropriate proportions. After a few days more growth, the result resembled real erectile tissue.
Next, Atala removed the corpora cavernosa from almost the entire length of the exterior part of the penises of 18 rabbits, leaving the nerves and urethra intact. He then replaced them with the engineered erectile tissues. Because the tissues were grown from the rabbits' own cells, there was no problem with immune rejection.
Once they had recovered from the surgery, the rabbits behaved... well, like rabbits. They attempted to have sex within 30 seconds of being put in a cage with a female. "They were able to copulate, penetrate and produce sperm," Atala told New Scientist. More detailed studies revealed that the penises generated about half of the normal pressure of an erect penis. "It's analogous to the penis of a 60-year-old man, versus that of a 30-year-old," says Atala. Details of the work will be published in the October issue of The Journal of Urology.
The team is now trying to improve the quality of the tissue, to make it comparable with that of a young animal. His lab is also trying to engineer entire penises, including nerves.
Using the collagen matrices was a major breakthrough, says Hunter Wessells of the University of Washington School of Medicine in Seattle, because there seems to be something special about the architecture of this matrix that guides the organisation of penile tissue as it assembles. When the technology moves to humans, the scaffolds could be taken from cadavers or made with a special three-dimensional printer that Atala's team has already used to create other structures.
However, it may be a while before the technique is tried with human tissue. And Atala says it will not work for female-to-male sex-change operations as women don't have the right cells. But the reconstruction techniques now used leave much to be desired. Aside from methods such as injecting fat cells, prosthetic devices are often implanted. These are expensive, prone to mechanical failure and can cause infections, says Wessells. "Plus it's not natural by any means."
BY SYLVIA PAGAN WESTPHAL
New Scientist issue: 14th September 2002
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