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Prenatal surgery offers hope
Medical researchers in Boston are hoping to use stem cells to help treat certain birth defects while the baby is still in the womb
Apr. 25, 2005
Toronto Star

When a mother-to-be learns the baby inside her has a birth defect, there is often little she can do.

But researchers in Boston say they may be able to start the healing process earlier by diagnosing and treating certain birth defects while the baby is still in the womb.

"When the baby is born you don't have time to engineer something and then fix it," said Dr. Dario Fauza of Children's Hospital Boston. "The defects are often times very severe."

Babies born with malformed tracheas, for example, face many serious challenges. If the rings of cartilage reinforcing the airway aren't properly constructed, the baby can suffocate, suffer brain damage and require prolonged hospitalization.

Doctors have tried to use cartilage from other parts of the baby to repair such defects, but Fauza said newborns don't have a lot of spare parts to begin with. Taking such a sample is also problematic, and often results in infections or the need for further surgery.

Fauza believes the tissues necessary to repair tracheal birth defects could be grown and implanted before birth, using a tiny bit of amniotic fluid. The liquid, which surrounds the fetus during pregnancy, contains stem cells that can produce a variety of skeletal and connective tissues.

"People always thought that amniotic fluid was just a deposit of dying cells ... but that's not true. They are very vibrant cells," Fauza said.

There are risks associated with drawing amniotic fluid from the womb. An amniocentesis can cause a miscarriage. But the procedure is often performed anyway for screening purposes. Fauza said all they'd need is a tiny amount of fluid from the screening sample to grow the necessary tissue.

Put these cells — known as mesenchymal stem cells — in the right substance and they'll generate cartilage.

Figuring out which substance will generate which cells involves a lot of trial and error, Fauza said. Subjecting mesenchymal stem cells to insulin growth factor might produce cartilage, while a mix of hydrocortisone and fetal horse serum might generate muscle cells.

"It's somewhat like cooking. Sometimes things work and sometimes they don't," he said.

Once the rings of cartilage are ready, a surgeon would implant them in the fetus' trachea using special tools and techniques. The objective is to operate without significantly disturbing the baby.

"The pregnant uterus does not like to be cut," said Fauza. "You are going to have to be very aggressive with medication to prevent labour."

Fauza uses a video camera to find his way around the uterus. The tiny lens of the camera is inserted into the uterus and fibre optic cables are used to illuminate the area. The guts of the camera equipment remain outside the body. Other tools Fauza uses were originally designed for surgery on the knee — another liquid environment.

Fauza has already has good success in animal studies. Rings of cartilage grown from ear cells were implanted in utero in five animals. All were able to breath properly at birth. Fauza is currently growing cartilage cells from amniotic fluid and hopes for similar results.

"The fetus heals much better in utero than after birth, for reasons we don't completely understand," Fauza said.

Fauza is even further along in his work on congenital diaphragmatic hernias. Fetuses with this birth defect have a hole in the tissue designed to separate the gastrointestinal system from the chest. If the stomach or intestines pass through this hole, it can impair the development of the lungs. Artificial materials currently used to repair hernias often tear.

As with tracheal defect repair, taking tissue samples from the baby can result in other health problems. Finding a suitable adult donor is tricky too; the risk of tissue rejection looms large.

Mesenchymal stem cells aren't as multi-talented as those derived from embryos. Embryonic stem cells can be coaxed into growing just about any kind of tissue in the body. Mesenchymal stem cells have a more limited repertoire.

But cells derived from amniotic fluid have certain distinct advantages. Fauza said they are very tolerant of low-oxygen environments — such as in the womb — which makes them ideal for growth in the lab. They are also easier to coax into producing tissue than adult stem cells.

Stem cells found in amniotic fluid are also far less controversial.

"You're getting stem cells that are more morally neutral because they are from a source that does not require the destruction of an embryo," said Tim Caulfield, Canada research chair in health law and policy at the University of Alberta.

"Although research shows Canadians support embryonic stem cell research, there are still some Canadians who have very strong views about the moral status of the embryo."

Caulfield doubts amniotic fluid will completely replace embryos as a source of stem cells — the latter offers too much promise to abandon embryonic stem cell research entirely. But amniotic fluid could prove to be a good alternative for certain treatments.

There are still unanswered questions about the ethical issues of prenatal surgery, Caulfield notes. For each kind of treatment, the risks associated with such a procedure have to be balanced against the benefits.

Fauza agrees that certainly not all birth defects warrant prenatal surgery. Hernia repair could be done after birth, for example.

But with spina bifida, he said "it's a very devastating defect. The children do so poorly." Paralysis, developmental problems and incontinence are common.

That's why Fauza is currently working on engineering a tissue with neural cells that could be wrapped around the spinal cord to try to repair the damage prenatally. Ultimately, Fauza believes he might be able to get those neural cells from the amniotic fluid too.

While Fauza still has much work ahead of him, his breakthrough techniques may one day mean that amniotic fluid will provide much more than a diagnosis. It might be the cornerstone for treatment.

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