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TISSUE ENGINEERING Amniotic Cells May Be Source of New TissueIn an ideal world, surgeons would have at their disposal an array of spare parts. Like mechanics, they could fix any malfunction or defect with a factory-made replacement. Although a repertoire of surgical tricks and the burgeoning field of tissue engineering are progressing toward this ideal, in many situations, surgeons are still working in a relatively empty shop. Pediatric surgeons trying to fix birth defects often face this supply problem, unable to borrow enough tissue from their tiny patients to repair abnormalities elsewhere on the body.
A scanning electron micrograph shows a synthetic scaffold at left that provides a degradable framework for engineered tissue. At right, the same scaffold has been seeded with human mesenchymal amniocytes that have formed tissuelike layers. Photos courtesy of Amir Kaviani The laboratory of Dario Fauza, HMS instructor in surgery at Children's Hospital and the Harvard Center for Minimally Invasive Surgery, sponsored by U.S. Surgical Corp., has been pursuing the goal of having a ready supply of fetal tissue on hand at birth to correct congenital abnormalities. "Many defects are actually repairable at birth without the necessity of a prosthetic patch," said Amir Kaviani, HMS clinical fellow in surgery in Fauza's lab. "But there are many instances—between 15 to 25 percent of cases—where the defects are so large they can't be properly closed." Often the surgeon uses a synthetic patch made of teflon, but it can tear out of the tissue and does not make as ideal a material as host tissue. In the past few years, Fauza's lab has worked to solve this problem by collecting a small amount of the fetus's tissue in utero and using the cells to engineer replacement tissue. The tissue has time to grow in culture while the baby comes to term and is ready for implanting at birth. In their latest study, the team has potentially sidestepped the need even for harvesting fetal tissue. Instead, they have found a source of usable fetal cells in an unlikely and much more accessible place—the amniotic fluid. Cellular Pearls"We used to think the amniotic fluid was sort of a garbage bag," Fauza said. But one person's trash is another's treasure, and the fluid has proved to be much more useful as a source of cells than was originally thought. Amniotic cells can be obtained from a small amount of fluid during amniocentesis, a procedure that is already often performed in many of the pregnancies in which the fetus has a congenital abnormality. "You cannot compare the risk of an amniocentesis with an actual fetal intervention. So it is a significant advantage," Fauza said.
Dario Fauza (left) and Amir Kaviani have found fetal cells in amniotic fluid that may help engineer needed tissue for surgery. Photo by Jeff Cleary The team first isolated fetal mesenchymal cells, which form the connective tissues of the body, from the amniotic fluid of sheep. They proliferated the cells in culture and seeded them onto a synthetic polymer scaffold that guides them to form tissuelike layers. The researchers repeated the experiment using human amniocytes, and Kaviani presented the results at a meeting of the British Association of Pediatric Surgery on July 20. So far, the cells seem to form dense layers equal to tissue engineered from samples of fetal tissue. In fact, the amniotic cells actually grew faster in culture than comparable fetal cells. "In general, even within fetal life, the earlier you go, the faster they grow," said Fauza. So it is possible that many of the cells were shed from the fetus earlier in development and retain the ability of younger cells to grow more rapidly. It is no surprise that fetal cells are in the amniotic fluid—after all, samples of the fluid are sometimes taken to determine the karyotype of the fetus. The common view is that the fluid is akin to bath water, but it is more than an external bath—the fetus drinks it, urinates it, secretes it from its lungs. "So all surfaces that are in any way in communication with the fluid end up potentially being sources for fetal cells," said Kaviani. Telling Tissue TypesFurther study may yield other kinds of cells that could be used to create a variety of tissue types. The immaturity of the cells, the researchers discovered, hints that amniotic fluid may include cells shed at early stages in development.Much needs to be done before the engineered tissue can be used in human surgery. First, the team must more thoroughly characterize the cells they have found, see how they differentiate in vitro and in animal models, and determine what sorts of tissue they can be used to create. "If we don't know what kind of cells they differentiate into, then the application for those tissues will be at the most, very vague," Fauza said. Another logistical hurdle is to identify the right kind of scaffold for each application from an array of possible materials. A scaffold must allow cell attachment and be able to withstand tension while remaining stretchable enough that it will not break away from the native tissue. While it needs to provide the structure for cells to form tissues, it must also allow blood vessels to grow into the site to provide oxygen and nutrients to the cells. If the tissue grown from the cells proves viable, it will put pediatric surgeons closer to an ideal situation. Once a defect is detected with ultrasound, they could take a few milliliters of amniotic fluid—even that much is enough to grow several hundred yards of tissue in a few weeks—and have a well-stocked shop when the surgery is performed. —Courtney Humphries |
