May lead to treatment for neurological diseases
By Edward Edelson
THURSDAY, Nov. 30 (HealthScout) -- Bone marrow stem cells can develop into working brain cells in living animals, two research teams report.
The findings raise the possibility of revolutionary treatments for neurological diseases such as Alzheimer's, Parkinson's and multiple sclerosis. But just as great as the prospects, so are the steps that still must be taken to make the possibility a reality, the researchers say.
"It will take many more people with more resources than I have," says Dr. Eva Mezey, chief author of one of the two studies, reported in the Dec. 1 issue of Science. She is chief of the In Situ Hybridization Facility of the National Institute of Neurological Diseases and Stroke (NINDS).
But the promise is there, based on a number if recent research findings. One is that the adult human brains can make new neurons, the active cells of the nervous system -- a feat long thought not possible. Another is that stem cells from one kind of body tissue can grow into cells of a different tissue. Experiments have shown that marrow stem cells can differentiate into neuron-like cells when grown in test tubes. Newer studies show the same thing can happen in mice.
Mezey studied female mice bred with no white blood cells. They received injections of bone marrow cells from normal male mice. Mezey followed development of the injected stem cells by looking for the distinctive male chromosome. That chromosome showed up in a significant number of neuron cells in several brain regions, demonstrating they were descendants of the injected cells.
"What is interesting is that even in adult animals, bone marrow stem cells are cells that can become anything," Mezey says. "What we need to figure out in the future is how the body makes them become neurons."
The second experiment, by a group led by Helen M. Blau, a professor at Stanford University, injected bone marrow cells engineered to express a distinctive green marker into adult mice whose marrow was destroyed by radiation. Again, the marrow-derived cells were found in several regions of the brain and functioned as neurons.
But what about humans?
The experiments raise two ultimate possibilities for medical treatments, Mezey says. One would use marrow stem cells from a person needing treatment: "We could take someone's own marrow, differentiate the cells and inject them into the brain."
Instead of whole cells, the second possibility would be to use the yet-unidentified molecules that change marrow cells into neurons. "We could figure out which growth factors in the brain make them become neurons, then speed up the process," Mezey says. "We would try to inject protein growth factors into the brain and let nature take its course."
She says one question that must be answered is whether the work in mice is transferable to humans. "I think this work is relevant to humans, but that needs to be proven. Primate work needs to be done," Mezey says.
Something else that has yet to be proved is that the new brain cells are in fact neurons, says Ron McKay, a NINDS neuroscientist. "You see cells in the brain that express certain features of neurons, but we don't know that they are neurons. We need to know if there are cells like this in the brain normally. People have to go in and characterize these cells more, ask if they are connected to other cells and so on," he says.
Work to answer these questions "is well under way," says Blau, who is professor and chair of molecular pharmacology at Stanford. Her group is looking at the properties of the new neurons, "seeing whether they connect with other neurons and communicate with them."
"We also want to understand the molecular signals that govern the marrow cells," she says, "We would like to understand what signals cause them to migrate to the brain, what signals cause them to change to neurons. We now have a whole team working on all the different aspects of this subject."
What To Do
Though groundbreaking, the experiments still require that methods be found to produce brain cells for specific diseases, McKay says. "If you have Parkinson's disease, this particular approach might be a decade away," he says.
The National Institutes
of Health has a primer on stem cells.