Functioning Neurons From Human Embryonic Stem Cells Produced
Science Daily — Scientists with the Institute of Stem Cell Biology
and Medicine at UCLA were able to produce from human embryonic stem
cells a highly pure, large quantity of functioning neurons that will
allow them to create models of and study diseases such as
Alzheimer's, Parkinson's, prefrontal dementia and schizophrenia.
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Researchers previously had been able to produce neurons - the impulse-
conducting cells in the brain and spinal cord - from human embryonic
stem cells. However, the percentage of neurons in the cell culture
was not high and the neurons were difficult to isolate from the other
cells.
UCLA's Yi Sun, an associate professor of psychiatry and biobehavioral
sciences, and Howard Hughes Medical Institute investigator Thomas
Südhof at the University of Texas Southwestern Medical Center were
able to produce 70 to 80 percent of neurons in cell culture. Sun and
Südhof also were able to isolate the neurons and determine that they
had a functional synaptic network, which the neurons use to
communicate. Because they were functional, the neurons can be used to
create a variety of human neurological disease models.
"Previously, the system to grow and isolate neurons was very messy
and it was unknown whether those neurons were functioning,
said. "We're excited because we have been able to purify so many more
neurons out of the cell culture and they were, surprisingly, healthy
enough to form synapses. These cells will be excellent for doing gene
expression studies and biochemical and protein analyses."
Sun's method prodded human embryonic stem cells to differentiate into
neural stem cells, the cells that give rise to neurons. When the time
was right, Sun's team added protein growth factors into the cell
culture that stopped the neural stem cells from self-renewing and
prodded them into differentiating into neurons.
To isolate the cells, Sun and her team added an enzyme that digests a
sort of protein matrix that holds cells in culture together. The
neurons could then be separated from the neural stem cells that had
not yet differentiated, a sort of chemical round-up that isolated the
neurons. The cells were then put into a cell strainer that allowed
passage through of the isolated neurons.
The large number of pure neurons produced will allow Sun and her team
to study their biological form and structure, the genes they express,
the development of synapses and the electric and chemical
communication activities within the synapse network.
"We will be able to study the cellular properties of neurons in a
very defined way that will maybe tell us what goes wrong in diseases
such as Alzheimer's and Parkinson's,
creating many models of human neurological diseases that may provide
the answers we're looking for. We don't know what causes prefrontal
dementia, Huntington's disease or schizophrenia. The key is likely in
the quality of neuronal communications. By studying the chemical and
electrical transmissions, we may be able to determine what goes wrong
that leads to these debilitating diseases and find a way to stop or
treat it."
Sun will be among the first researchers to be able to study true
neuron function.
A second important discovery in Sun's study showed that two embryonic
stem cells lines derived in similar manners, and therefore expected
to behave similarly when differentiating, did not. Using the same
techniques to prod the two embryonic stem cells lines to
differentiate, Sun found that one line had a bias to become neurons
that are found in the forebrain. The other line differentiated into
neurons found in rear portions of the brain and spinal cord. The
finding was surprising, and significant, Sun said.
"The realization that not all human embryonic stem cell lines are
born equal is critical," Sun said. "If you're studying a disease
found in a certain part of the brain, you should use a human
embryonic stem cell line that produces the neurons from that region
of the brain to get the most accurate results from your study.
Huntington's disease, for example, is a forebrain disease, so the
neurons should be differentiated from a cell line that is biased to
produce neurons from the forebrain."Sun said there are ways to prod
an embryonic stem cell line biased to become neurons found in the
rear brain to become neurons found in the forebrain. However, there
are limits to how much prodding can be done.
Sun and her team confirmed that the two embryonic stem cell lines
were different through gene expression analysis -- neurons that
perform different functions in different parts of the brain express
different genes. The cell line prone to becoming neurons found in the
forebrain expressed genes typically found those neurons, while the
other line expressed genes found in the rear brain and spinal cord.
Sun and her team now are studying why the two human embryonic stem
cell lines have biases to become different types of neurons.
"If we knew that, we might be able to tweak or alter whatever is
driving the bias so that limitation in the stem cell line could be
bypassed," Sun said.
Study results were recently published in an early online edition of
the journal Proceedings of the National Academy of Sciences.
Note: This story has been adapted from a news release issued by
University of California - Los Angeles.
http://www.scienced
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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