The quest to make body parts in the lab has just taken a big step forward. Scientists have successfully transplanted laboratory-made vaginas into four teenage girls whose own were absent because of a rare disease.
Scientists have successfully transplanted laboratory-made vaginas into four teenage girls whose own were absent because of a rare disease, marking a milestone in the quest to grow structurally complex body parts.
The experiment was published Thursday in the journal Lancet along with another study, in which a separate group of researchers transplanted lab-made nostrils into patients whose noses were damaged by cancer.
The vaginas were created from the patients’ own cells and implanted between 2005 and 2008. Today, the women report normal sexual function.
“This sort of regenerative medicine is pushing forward,” said Alexander Seifalian, a professor of nanotechnology and regenerative medicine at University College London, who wasn’t involved with the studies. The experiments are significant because both the vagina and nostril are tricky to engineer, and no lab-made versions had been successfully transplanted into patients before.
Some of the easiest organs to make are flat structures, like skin, typically composed of a single type of cell. Tubular body parts including windpipes, urethras and blood vessels are harder to fashion as some are typically made of two cell types. But in recent years several such organs have been successfully transplanted into patients.
Another step up in complexity are body parts such as the vagina, a highly elastic organ that also secretes mucus. And the final frontier is the quest to make solid organs—such as the heart and liver—that typically don’t have a cavity and have more complex functioning.
“We have seen the implantation of the first three types but solid organs are exponentially more complex,” said Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in Winston-Salem, N.C., and leader of the team that did the vagina transplants. “It’s still going to be a while” before a lab-grown solid organ is put in a person, he said.
Dr. Atala began the effort to make a lab-grown vagina in the late 1990s to address disorders that cause some girls to be born without normal vaginas. Cancer and trauma can also lead to vaginal damage or loss. Currently, doctors reconstruct the vagina using a patient’s own skin or part of the intestine, but both cause other physical problems.
The effort immediately hit a roadblock: “We couldn’t even get the vaginal mucosal cells to grow outside the body,” Dr. Atala recalled. After solving that problem, the team needed to find something to serve as a scaffold—or skeleton—on which the cells would sit. They rejected various options, including the material used to make surgical sutures, before settling on one they liked: tissue from a pig’s intestine.
The pig tissue was first bathed in detergent, which removed the original cells and left behind a scaffold-like structure made from collagen. This was coated on one side with epithelial cells, which line the body’s cavities, and which had been obtained via a biopsy of the patient’s external genitals. The other side was coated with smooth muscle cells, also from the patient. When the scaffold was placed in an incubator and nourished with chemicals and oxygen, the cells began to grow.
The scaffold was hand-sewn into a vagina-like shape and tailored to fit the patient. Surgeons created a cavity in the patient’s pelvis and sutured the cell-populated scaffold to reproductive structures, including the uterus.
The procedure was done on four girls who were between 13 and 18 years old. They were born with Mayer-Rokitansky-Küster-Hauser syndrome, a rare genetic condition in which the vagina and uterus are underdeveloped or absent. Lacking the organ, they had no sexual function and couldn’t menstruate.
The surgeries were performed at the Metropolitan Autonomous University in Mexico City between June 2005 and October 2008. The layers of cells on the scaffold weren’t fully formed but, gradually, blood vessels emerged and then nerves started to develop. How the body does this is a central mystery.
“The blood vessels and nerves come on their own,” Dr. Atala said. “The body’s ability to regenerate is amazing if you put the right ingredients there.”
More than eight years after the first surgery, all the women report normal sexual function, including lubrication and painless intercourse. Two of them have uteruses and could potentially get pregnant via intercourse, Dr. Atala said.
In a separate experiment, a team led by Ivan Martin of the University of Basel in Switzerland used a similar technique for reconstructive surgery on the nose, the most common site of non-melanoma skin cancer. The tumor can be cut away, but that may also require removing a large part of the nostril. Typically, surgeons add the missing piece by grafting cartilage taken from elsewhere, such as the patient’s rib, ear or nasal septum. However, this involves a second operation that can be painful.
Now, for the first time, Dr. Martin’s team has demonstrated the rebuilding of the nostril with lab-made cartilage instead of the grafting technique. His method was used successfully on two women and three men between the ages of 76 and 88.
The researchers first removed cartilage cells from the nasal septum of each patient and grew them in a lab dish. When the material was large enough, it was sculpted according to the defect and implanted.
“The cartilage acts as a scaffold and within six months” the thick, fibrous tissue of which the nostril is made, naturally grows upon it, said Dr. Martin. As with the grafting technique, the final touch is to transfer a bit of skin from the forehead to where it is now needed on the nose.
The rebuilt nostril works just as well as the real thing, but there is a small cosmetic glitch: Because the skin is taken from the forehead, Dr. Martin said, it has a different color than the rest of the nose.
Credit: The Wall Street Journal, 2014