April 15, 2002
Neural Stem Cells Can Develop into Functional Neurons
Researchers have found that neural stem cells isolated from the
brains of adult rats can mature into functional neurons. Stem cells,
which are found in tissues throughout the body, are immature progenitor
cells that give rise to more specialized cells that form tissues and
organs.
The scientists emphasized that although their studies show that
adult stem cells have the capacity to develop into functioning brain
cells, their findings do not mean that clinical application of adult
neural stem cells is imminent. The studies were published April 15,
2002, in an advance online article in Nature Neuroscience by
Howard Hughes Medical Institute (HHMI) investigator Charles
F. Stevens and colleagues Hong-jun Song, an HHMI research
associate, and Fred H. Gage at The Salk Institute.
“It may be that, for reasons we don’t yet understand, adult stem cells will never be useful in therapy and that we will always need embryonic cells. Or, it may be the other way around. We just don’t know.”
Charles F. Stevens
According to Stevens, previous experiments showed that adult neural
stem cells bear certain molecular markers that suggested that they
could become neurons. “It’s absolutely clear that embryonic
stem cells can make perfectly good neurons, otherwise there would be no
development of the brain,” said Stevens. “But nobody had
demonstrated before that adult stem cells can generate fully functional
neurons, beyond just having particular protein markers.”
To see whether adult neural stem cells possessed the ability to
develop into functional neurons, Gage and his colleagues first isolated
stem cells from the hippocampal region of the rat brain and then tagged
the cells with fluorescent molecules that made it possible for the
researchers to track the stem cells as they developed. The scientists
“co-cultured” these tagged cells along with normal adult
neurons on a carpet of supporting cells called astrocytes, which are
known to produce chemical signals that trigger neuronal growth.
“The normal neurons were necessary to show that our
stem-cell-generated neurons were genuine, in the sense that they could
incorporate into the neural circuitry that attempts to become
established in cell culture,” explained Stevens.
In their initial studies, the scientists found that the
fluorescently tagged stem cells developed normal neuronal structures,
including the long, cable-like axons and branching dendrites that form
connections with other neurons. The researchers observed that the axons
and dendrites produced protein markers that were characteristic of
normal neurons.
By recording electrical signals from the cultured cells when they
were stimulated, the scientists observed that functioning connections,
called synapses, were established between the stem-cell-derived neurons
and normal adult neurons. Synapses are the junctions between neurons
where nerve impulses are transmitted. Electron microscope studies of
the synapses revealed that they appeared normal.
The researchers also showed that the stem-cell-derived neurons
produced neurotransmitters, chemical signals by which neurons
communicate to each other across synapses.
“However, we did find that the stem-cell-derived neurons did
not make as many synapses as normal neurons,” said Stevens.
“It might be that adult stem cells by themselves don’t give
rise to cells with sufficient synapses; that we didn’t give them
the right environment for synaptic production, or that these particular
cultured cells might have contained mutations that reduced synapse
production.”
To test whether astrocytes played a role in triggering the
maturation of adult neural stem cells, the scientists cultured the
cells with both neonatal and adult astrocytes. The studies showed that
both types of astrocytes produced factors that supported stem cell
maturation.
According to Stevens, the observation that adult neural stem cells
can mature into functional neurons could have clinical implications.
“There has been considerable debate about whether adult neural
stem cells, as well as embryonic stem cells, could be used to
regenerate damaged brain tissue,” he said. “These findings
give some indication that if we ever reach the point where stem cell
therapy is feasible to treat such disease, there’s some hope that
adult stem cells might work.”
But Stevens emphasized that extensive comparative studies of both
embryonic and adult neural stem cells will be needed before their
relative advantages and disadvantages can be determined.
“It is absolutely vital to continue research using embryonic
neural stem cells,” he said. “It may be that, for reasons
we don’t yet understand, adult stem cells will never be useful in
therapy and that we will always need embryonic cells. Or, it may be the
other way around. We just don’t know.”
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