March 23, 2005
Chick Embryos Turn Human Bone Marrow Stem Cells Into Neurons
Cells taken from human bone marrow and transplanted into chicken embryos in place of chicken spinal cord nerves were converted into nerve cells.
The Norwegian team used a micro-surgery technique to cut out a small section of the developing spinal cord within the chicken egg.
Human haematopoietic stem cells (hHSCs) from bone marrow were then implanted into the damaged area.
The eggs were incubated before the embryos were removed, and spinal cord slices containing human cells dissected out and analysed.
These neurons were found to be very functional and even have the ability to send signals to other neurons.
Put human haematopoietic stem cells into the right environment and they will become neurons.
Senior researcher Joel C. Glover, of the Institute of Basic Medical Science at the University of Oslo, in Norway said, "We found that bone marrow stem cells did make neurons in the environment of the regenerating embryonic [chick] spinal cord."
There are a number of types of neurons. While the news reports on this study do not say what types of neurons were produced I'm going to guess that they were cholinergic. Parkinson's Disease sufferers need dopaminergic neurons. However, getting the bone marrow stem cells to turn into any kind of neuron is probably the bigger obstacle to get past than getting them to turn into a particular type of neuron. So this result is good news for Parkinson's sufferers.
One obvious next step is to try to discover which compounds in the chick spinal cord area are stimulating the bone marrow cells to turn into neurons.
The key to the success of this model lies in as-yet-unidentified compounds within the quickly developing "microenvironment" of the embryonic spinal cord, said Paul Sanberg, a professor of neurosurgery and director of the University of South Florida's Center for Aging and Brain Repair.
Sanberg, an expert in this kind of research, believes that if scientists can identify those compounds, they might then be able to use them as a kind of cellular fertilizer -- encouraging adult stem cells to generate into human neurons.
Sanberg also commented that since chicken eggs are used on a massive scale to make vaccines (notably influenza vaccine - and that method is too slow to handle deadly pandemics btw) that the infrastructure and considerable experience already exists for using chicken embryos to make suitable cell types for therapeutic purposes.
The ability to take an adult stem cell type and turn it into a differentiated cell type which it does not normally become is strongly suggestive that adult stem cells can be made quite pliable if only scientists can discover the right combinations and concentrations of growth factors to change them. I've always expected this to be the case. But the question has always been just how hard will the search turn out to be to discover the compounds and techniques for converting adult stem cells into a larger range of cell types? Perhaps experiments with chick embryos will provide the means to more rapidly discover how to change the differentiation state of adult stem cells.
While the use of human embryonic stem cells (hESCs) remains morally objectionable in some quarters it is important to note that the use of hESCs may still be a faster approach for the development of some forms of cell therapies. However, even if hESC research is slowed by political opposition it is my very strong expectation that for any therapy that can be developed using hESCs eventually a way will be found to provide an equivalent therapy using adult stem cells instead.
One other point is too often missed in the adult versus embryonic stem cell debate: A larger research effort (meaning more money) would accelerate either of these approaches. I wish as much effort would go into pushing for increased stem cell research funding (even if that funding would come with strings attached with regard to use of hESCs) as currently goes into arguing about hESC research. Lots of questions about stem cells can be answered with research into animal models and lots of progress can be made with adult stem cell research.
Researchers have recently reported remarkable results with adult stem cells at Griffith University in Australia. There is an article discussing the work in The Australian here, and there is an article on the CNN website here. Below is an excerpt:
"Our experiments have shown adult stem cells isolated from the olfactory mucosa have the ability to develop into many different cell types if they are given the right chemical or cellular environment," explains Mackay-Sim. New nerve cells, glial cells, liver cells, heart cells, muscle cells - all were grown in a dish from stem cells from the human nose. Establishing the versatility of these adult stem cells was in itself a significant scientific achievement, but the Griffith University team's experiments also uncovered a raft of additional advantages.
For starters, such cells are easily harvested. The research team's doctor, prominent Brisbane ear, nose and throat specialist Chris Perry, was able to extract them from consenting patients - and later from the scientists themselves - by simply spraying the inside of the nose with a local anaesthetic and then removing a sample no bigger than a grain of pepper. The harvested stem cells were not only readily available but proved to be astonishingly easy to grow in the laboratory, with millions of them forming within weeks.
Of course, this work must be replicated and the functionality of the derived cells must be tested before one can judge the importance of this work. But it does sound exciting.
Randall Parker said: “One other point is too often missed in the adult versus embryonic stem cell debate: A larger research effort (meaning more money) would accelerate either of these approaches.”
Note, California will have $3 billion to spend on stem cells because its voters passed a ballot initiative called “Proposition 71”. The California Supreme Court just dismissed two lawsuits trying to block the implementation of the “Proposition 71” as reported here">http://www.reuters.com/newsArticle.jhtml?type=scienceNews&storyID=7990969">here. The main boosters of the initiative were interested in supporting embryonic stem cell research. It will be interesting to see the type of research supported by the “California Institute for Regenerative Medicine”, the organization created by the initiative
California Prop 71 does seem it will really boost the field. It's $300 million per year is more than NIH itself spent in 2003: $215 million ($190m aESC, $25m hESC). Additionally, the prop seems to have jump started a number of other states into stem cell research funding initiatives, such as Pennsylvania, New York, New Jersey, Florida, Texas, Illinois, Massachusetts, Wisconsin, Washington, and New Hampshire.
One other point is too often missed in the adult versus embryonic stem cell debate: A larger research effort (meaning more money) would accelerate either of these approaches.
Is that true? Doesn't it pre-suppose that there are people with the necessary training and credentials who aren't already doing research in the field who would be attracted into the field? Are there? If not, more money could paradoxically result in less research being done.
The irony of the federal restrictions on human embryonic stem cells is that their likely net effect appears to be to cause a far larger expenditure on stem cells than would otherwise be the case. The competition between the states looks set at this point to produce more total money for stem cells than ever would have been appropriated at the federal level had Bush put no restrictions on human embryonic stem cell research.
Yes, there is a huge amount of unused research capacity in the United States. A lot of grad students, post-docs, and faculty do menial labor that could just as well be done by lab techs. I think the ratio of menial work to brain power is much too high in the sciences.
Also, a lot more engineering talent could be pulled into the field to automate it. I favor much more funding for the development of instrumentation and lab automation technology.
I read Fumento's article when it first came out. He's summarizing from a number of studies but I think he's painting an excessively rosy picture about adult stem cells.
First off, some of the adult stem cell therapy successes have turned out to work by cell fusion. The cells did not change into the needed target type. There is a limit to what cell fusion can accomplish. When cell fusion helps it is great. But the discovery that cell fusion was the mechanism by which adult stem cells work in some cases certainly puts a limit on what those cells can accomplish. For example, when large numbers of heart muscle cells have already died then saving some of the remaining ones with cell fusion will not be enough in all cases.
Second, adult stem cells have some limited abilities to change into subranges of cell types. But some of the early reports on changing adult stem cells into cell types which they do not normally turn into have since been discredited as a result of better techniques for assaying cell types and other improvements in lab technques.
Third, not all the published studies that have reported successes have turned out to be repeatable. Some had small sets of patients and were not statistically significant. Some had poorly chosen clinical end points for measuring success.
We need ways to turn adult stem cells into more types of cells. So this latest report is very important.
Journalism recounting advances in stem cell research sometimes has a strong political slant. The Fumento article cited by Mark Macedon depicts very positively the use of adult stem cells from bone marrow to improve heart function after heart attacks. A more critical report on the same research appeared in the New York Times in an article entitled "The Uncertain Science of Growing Heart Cells" located here. Here is an excerpt:
At least two separate laboratories, at Stanford University and at the University of Washington in Seattle, reported last year that they had been unable to repeat the Orlic-Anversa experiment. Bone marrow stem cells, these researchers found, did not turn into heart tissue. The few that lodged in the heart turned into blood cells in the usual way. The Stanford researchers, who included Dr. Irving Weissman, a leading expert on the blood's stem cells, warned that until the science underlying the clinical trials was better understood, ''these studies are premature and may in fact place a group of sick patients at risk.''
However, the New York Times does admit that multiple clinical studies have shown improvement of heart function when adult stem cells are used therapeutically. There seems to be some mechanism that allows the adult stem cells to help the healing process. Here is an excerpt:
Clinicians say they have established that the technique is safe -- some 200 patients have now been treated worldwide without adverse effect -- and that the results so far are worth pursuing. But individual cases, however striking, count less than overall statistics. Most studies so far show a 5 percent to 10 percent improvement in heart function. While not great, that is not discouraging, either, given that most of the patients were very sick to begin with.
Interestingly, the Stanford researcher, Irving Weissman, quoted above who says that the heart studies are “premature” is a major advocate of embryonic stem cell research as shown in this profile
that appeared in the Economist. He has also done considerable research with adult stem cells.
I think Irving Weissman works only with adult stem cells in fact. See my previous posts about Irving Weissman here and here. For some interesting insights and an overview of the state of stem cell research see Weissman's July 14, 2004 testimony on adult stem cell research to the US Senatoe Committee on Commerce, Science, & Transportation.
Randall Parker said: "I think Irving Weissman works only with adult stem cells in fact."
The Economist profile from 2003 said: "Until now, Dr Weissman's work has been all about adult stem cells - though that may soon change. At Stanford's new Cancer and Stem-Cell Biology Institute, he plans to encourage the creation of new embryonic stem-cell lines." So I thought he might have done some research with embryonic stem-cells by now. His Senate testimony indicates that he advocates research in multiple avenues in parallel, e.g., adult tissue stem cells, embryonic stem cells, and nuclear transfer stem cells. In any case, thanks for the pointers. I did read your comments about the proposed human-mouse chimera when you posted them earlier this month. (I appreciate the skill, intelligence and work that are required to run this website. Thanks for your great efforts.)
Two responses to Randall Parker, with second posting first. Irving Weissman is among those who research adult stem cells exclusively to attempt to disparage previous research. Douglas Melton of Harvard is another. For example, Weissman and colleagues claimed in Nature that because THEY could not convert marrow cells into anything else it simply couldn't be done.
See my article: http://www.fumento.com/biotech/outlookstem.html
The typical media reaction was UPI's "Promise of Adult Stem Cells Put in Doubt." Weissman eschewed the usual cautionary scientific terminology such as "it appears" or "evidence indicates," or "our particular study has found." Instead he smugly told UPI: "They [the cells] don't make brain; they don't make heart muscle or any of these things." Scientists don't phrase things like that; advocates do. In any event, go to PubMed and you'll find that countless researchers since then have done what Weissman CLAIMS he failed to do. Weissman's work tells us much about Weissman; nothing about stem cells.
Likewise, the fusion stuff came from anti-ASC advocates. Again, go to PubMed where you'll find one study after another explicitly stating that the therapeutic results from ASCs was NOT from fusion although certainly some fusion can take place. I don't think even Weissman goes with the fusion stuff anymore. It's settled. Again, see my above article.
Regarding the "discrediting" of reports that ASCs can be differentiated outside of their own germ layers, this reflects the cottage industry of doing research for no other reason than to discredit. It remains that at least four labs have published data showing the conversion of marrow cells into all three germ lines, with the most recent just in February from the Tufts lab of Dr. Douglas Losordo. Not incidentally, after Losordo first reported his results a few years ago they were "discredited." By whom? Douglas Melton, who again played the game of "If I couldn't do it, it can't be done." Now who's discredited?
As to the third point, of course not all the human studies have either been replicable or replicated yet. But almost countless studies have grown human heart muscle and blood vessels from marrow stem cells. Recently a German girl had a huge gap in her skull filled in with marrow stem cells, while a German man had his jaw replaced with similar cells. Remember that Weissman said none of this could be done. Another fascinating development is Harvard's Dr. Denise Faustman growing pancreatic islet cells in rodents from spleen stem cells. She literally cured the mice of diabetes.
For more, see my most recent articles:
An example of apparent media bias appears in an article in today’s New York Times. It discusses stem cell research but never once mentions the existence of adult stem cells. Any reader without a background in the subject would probably assume that “stem cell research” is synonymous with “embryonic stem cell research”. The article states
Under a policy set by President Bush in August 2001, federal research financing is available only for the finite number of stem cell lines in use before that time, a number initially thought to be about 60 but now thought to be 22.
However, this quote properly refers only to restrictions on embryonic stem cell lines. The reporter omits the key word “embryonic” from the phrase “finite number of stem cell lines”. This is misleading because adult stem cells are not mentioned anywhere in the article. Many readers will not realize that federal research funds are available for stem cell lines based on adult stem cells. Further, there is no federal numerical cap on stem cell lines derived from adult stem cells.
Yet, the NY Times is not monolithic. The newspaper presented an admiring article by reporter Gina Kolata describing the work of Denise Faustman on diabetes. Faustman's research reveals the remarkable capabilities of adult stem cells in the pancreas (and the drug BCG). (Fumento mentions this work above.) The Kolata article is reprinted at the Iacocca Foundation website here.
Weissman has part ownership in a few companies that are developing stem cell therapies based on adult stem cells. I seriously doubt he has spent several years of his life as a scientist to do research to disprove the usefulness of what he is doing commercially.
I agree that the the media frequently misrepresents embryonic stem cell research as being all stem cell research. I always try to include the right qualifier when talking about stem cells and repeatedly try to clarify to my readers that there are multiple kinds of stem cells and that only one type is meeting serious political opposition.