After seven years of toiling, scientists at the Wake Forest University School of Medicine and Harvard School of Medicine report they have isolated stem cells from a new source: amniotic fluid. The researchers not only succeeded in separating the progenitor cells from the many cells residing in the watery fluid in the placenta surrounding an embryo, but were also able to coax the cells to differentiate into muscle, bone, fat, blood vessel, liver and nerve cells.
According to lead author Anthony Atala, director of Wake Forest's Institute of Regenerative Medicine, 99 percent of the U.S., population could conceivably find genetic matches for tissue regeneration or engineered organs from just 100,000 amniotic fluid samples. In its research, the team isolated stem cells via amniocentesis--a common procedure performed about 16 weeks into pregnancy during which amniotic fluid is drawn to test for genetic disorders in a fetus--as well as from the placenta after birth. The researchers write in their paper--published in this week's Nature Biotechnology--that stem cells make up 1 percent of all the cells in amniotic fluid samples.
"It's been known for decades that there are cells in amniotic fluid," Atala says. "The embryo is constantly shedding all these cells, as it's developing, to the amniotic fluid. The baby's actually breathing in, swallowing the fluid, and it's all coming out through all the pores and gets trapped in the placenta."
After isolating the cells, Atala and his team introduced growth factors to different cell lines in an attempt to assess their potency. They were able to get the amniotic fluid-derived stem (AFS) cells, to transform into many different types of tissue found in fat, blood vessels, liver, muscles and bone as well as the central nervous system. This range comprises all three embryonic germ layers: the mesoderm, the progenitor of bone, muscle and connective tissue; the endoderm, which develops into digestive organs as well as the lungs; and ectoderm, which becomes nerves, skin and the brain. In addition to laboratory experiments, the team studied AFS cells in mouse models, grafting neural stem cells into the brains of mutant mice with disrupted neural development and growing bone tissue in another set of immunodeficient mice.
"It adds to the list of pluripotent stem cells that have already been identified in other sources and tissues," says Willem Fibbe, an immunohematologist at Leiden University Medical Center in the Netherlands. "If these cells have this potential, what would be the specific reason to prefer amniotic fluid-derived cells over the umbilical-cord-derived cells, over the [fat-] tissue-derived cells and the bone-marrow-derived cells?"
Atala says that compared with other types of pluripotent stem cells--save embryonic stem cells--AFS cells are "truly pluripotent" and that their major advantage is that after two weeks of culturing they expand quickly, doubling every 36 hours so that they are in large supply. When compared with embryonic stem cells, AFS cells have two main advantages: First, no embryo needs to be harmed in harvesting the cells, sidestepping a major, hot-button political issue. Also, as Atala points out, AFS cells will not form tumor cells, as the considerably more raw embryo-derived cells can.
"They're not as early and they're not as wild," he explains. "The cells are further along the line of development--and you don't see fetuses developing tumors--so these cells are much more controlled." Atala adds that the AFS cells lie between embryonic and adult stem cells in that the former expand quickly, but can develop into tumors, whereas the latter will not become cancerous, but grow exceedingly slowly.
"The new paper by Atala's group is indeed a breakthrough in demonstrating such a high potential for therapy of a specific set of stem cells in amniotic fluid," observes Markus Hengstschläger, a geneticist at the University of Vienna who is part of the group that, in 2003, first identified the presence of stem cells in amniotic fluid. "It is always a very important question to determine the real potential of such cells."
Going forward, Atala plans to study therapeutic uses for the AFS cells as well as attempt to coax them to differentiate into the tissue found in the heart, pancreas and kidneys. "We still don't know what the benefits are of all these cells--all cells have their strengths," Atala says, referring to all different stem cell types. "We need to keep studying all these different cell types to see what works best for each application at the end."