In January, scientists generated national attention in the mainstream press when they announced that they had discovered stem cells in amniotic fluid, and proposed that the cells could morph into brain, muscle, and bone marrow tissue. But neurologists have questioned the strength of the research for brain cells, and a study author said more work is needed.
The study, published online in advance of the print publication of Nature Biotechnology, was heralded as a possible alternative to highly controversial embryonic stem cells.
Embryonic cells are considered the most basic building block of human development. It is from these cells that the body develops, and researchers believe that stem cells could lead to solutions, if not cures, to many diseases and injuries, including Parkinson disease and spinal cord injuries.
However, embryonic stem cells come from destroyed human embryos that have been fertilized in vitro, and remain unused, frozen, and donated for research. President Bush has limited the number of embryonic lines that can be used for research, claiming that harvesting involves the loss of life.
On the other hand, amniotic stem cells are simply drawn from the fluid found around a living fetus as part of an amniocentesis, which is done on older mothers or those particularly at risk for birth defects.
In the study, investigators from the Wake Forest Institute for Regenerative Medicine tested lines from 19 amniocentesis donors and found that the cells generated several different lines, including engrafting a developing mouse brain to produce neural stem cells.
One of the authors, Evan Snyder, MD, PhD, said many reports overstated the study's research. It is important work, he said, and an exciting development because the cells are easier to grow in a laboratory, there are fewer ethical concerns surrounding the cultivation, and they did not grow tumors after several months.
“The more significant findings were achieved with the bone marrow and muscle tissue,” said Dr. Snyder, director of the Stem Cells and Regeneration program at The Burnham Institute for Medical Research. “I think it takes more time to mature into appropriate neurological cells and more time to have a neurological payoff.”
The study said cells were positive for surface markers characteristic of neural stem cells, but not all embryonic stem cells. Researchers said the grafted cells dispersed through the host mouse brains and survived for at least two months in several different brain areas, including the hippocampus and olfactory bulb.
But neurologists said that they were concerned that the amniotic stem cells simply left markers, and did not completely morph into neural cells.
“I think they have an interesting cell and they got it to grow for a long time,” said Clive Svendsen, PhD, co-director of the Regenerative Medicine program at the University of Wisconsin at Madison.
“But I thought the brain data did not show good integration into the brain – if the cells had migrated throughout, they would not be collected around the ventricular surface.”
What the study needed, he said, were good images of cells double labeled with the markers, showing that they had taken the form of brain tissue.
Hongjun Song, PhD, assistant professor of neurology in the Institute for Cell Engineering at Johns Hopkins University School of Medicine, said the cell looked differentiated, but did not seem to be a functioning neuron yet.
“It's not sufficient to show a few markers and claim it's a neural cell,” he said.
The study did have a stronger basis for the amniotic cells developing into other tissues, particularly bone, researchers said. They said bone is a relatively simple structure, whereas brain tissue is more difficult to develop and they wondered whether, with more time, the cells might have developed stronger neural features.
Dr. Song, who studies how neural stem cells give rise to neural cells, said the next step would involve a longer time table to see if the cells continue to develop into working neural tissue.
“They need to look at how many cells are still in a cell cycle at a given time,” he said. “Can they do it? Can they become neurons? And if they can, what's the best way to use them?”
Dr. Snyder said he agreed completely and that the plan was to run trials in a greater number of animals and observe them for a longer period of time. He said he had spoken to the study's lead author about including dose response curves, where researchers administer an increasing number of cells more and more frequently at various time points and locations.
Although he was excited about the paper's results, he thought the reports about the study are “over-hyped and misinterpreted in my view.”
Dr. Snyder said he intended to discuss the early stages of discovery of the amniotic stem cells and their potential use. One of the more exciting discoveries, researchers said, was not just how broadly multipotent the cells were, but that they also included both an “X” and a “Y” chromosome, showing that they came from the baby, and not from the mother.
“We're not at the stage where they've become functional cells in the brain,” said Dr. Snyder. “We've showing that they can engraft into the brain, they don't cause tumors or rejection and don't cause deformation, but we're not sure yet whether we are able to go beyond that.”
The next step, Dr. Snyder said, is to put the amniotic stem cells “head to head” with embryonic stem cells and bone marrow stem cells and see what works best for which tissues.
“You want to know how they stack up against each other… do they do worse or better or the same,” he said. “And the only way to do that is to have a bake-off for stem cells.”
All three researchers said the Nature Biotechnology study was a good first step in the right direction.
“It's definitely an interesting finding,” said Dr. Song. “We may be going down the road, but we're not there yet. We just have to be patient.”