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Growing neurons for experiments

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Growing neurons for experiments

Postby TwistedHelix » Tue Aug 21, 2007 7:39 am

I think we're all pretty disillusioned by the failure of animal models to provide an accurate experimental analogue of human MS. Hopefully this new development will provide a better tool for understanding the disease, as well as more relevant test results.


Main Category: Neurology / Neuroscience News
Article Date: 20 Aug 2007 - 13:00 PDT
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.

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.

The study results were published in a recent early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.

"Previously, the system to grow and isolate neurons was very messy and it was unknown whether those neurons were functioning," Sun 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," Sun said. "We're currently 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.

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Article adapted by Medical News Today from original press release.
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The Institute for Stem Cell Biology and Medicine was launched in 2005 with a UCLA commitment of $20 million over five years. With more than 150 members, the ISCBM is committed to a multi-disciplinary, integrated collaboration of scientific, academic, and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The institute supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The institute is a collaboration of the David Geffen School of Medicine, UCLA's Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College.

Source: Kim Irwin
University of California - Los Angeles
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Postby gwa » Tue Aug 21, 2007 8:40 am

Dom,

This goes on my list of the top 10 things I have seen in research that may help MS patients.

I am at the point that when I read the word "mouse" I just ignore the research that is being relayed.

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Postby TwistedHelix » Tue Aug 21, 2007 12:43 pm

gwa,
I tend to agree. Since it's all we've got for now I try to think of it as having an outdated road map – – shabby, faded, worn out and virtually useless *, but with a bit of luck it might just point us in the right direction.

* also a valid description of me.
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Postby Lyon » Tue Aug 21, 2007 3:15 pm

TwistedHelix wrote:shabby, faded, worn out and virtually useless *, but with a bit of luck it might just point us in the right direction.
* also a valid description of me.
Hi Dom,
Being the terribly close friend that I am, I have to strongly differ with your comment because my definition of the word "useless" is not nearly as rigid as yours :twisted:
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Postby CureOrBust » Wed Aug 22, 2007 5:53 am

I see them as being a long way off, but heading in a positive direction. My view is formed because they are just making neurons for now, and myelin appears to play a big role in this disease.
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Postby Lyon » Wed Aug 22, 2007 6:06 am

You're right Cure. Regardless of one's personal opinion of what is happening in the disease process, regardless of which stage of the disease process one has a personal interest in, neuroregeneration is a very important issue.

Although not the "cure" I'd envisioned, I've even read that, in the absence of being able to stop the disease process, being able to regenerate neurons quicker than ms degenerates them might be considered a sort of "cure".

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Postby TwistedHelix » Wed Aug 22, 2007 7:11 am

Bob,
I can't work out if your previous comment was an insult or a compliment, so being the mature, calm and dignified person that I am I'll maintain a regal silence.
The idea of being able to repair tissue faster than MS can damage it is a very odd one: it would raise the prospect of being able to live a life with MS and even to improve, while never actually getting rid of the disease.
Given the" toxic environment" which Bromley's neurologists often describes, wherein the body's own repair mechanisms are prevented from working either by substances or signalling, and assuming that that environment is part of the nature of MS, it's hard to see it happening, but then again stranger things have happened.
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Postby Lyon » Wed Aug 22, 2007 12:23 pm

TwistedHelix wrote: I can't work out if your previous comment was an insult or a compliment, so being the mature, calm and dignified person that I am I'll maintain a regal silence.
Hi Dom,
Gosh, if you put it in terms of compliment or insult I'd have to lie and say that it was meant to be a compliment because I only wanted to pick on you and not actually insult you!
TwistedHelix wrote:The idea of being able to repair tissue faster than MS can damage it is a very odd one: it would raise the prospect of being able to live a life with MS and even to improve, while never actually getting rid of the disease.
I agree that it is odd and when I read the article for the first time 6 or 8 months ago I remember thinking that it was a concept I'd never considered...but does seem to have truth to it. Repairing the damage at an equal or higher rate than the damage accrues would seem to prevent progression.

At any rate, this is likely a moot point because stopping progression sure looks to be much closer than neural regeneration.

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