ES Stem Cells Become Neurons: May Not Be Pluripotent
This PR press release contains two stories instead of one: First, researchers at UCLA apparently morphed embryonic stem cells into neural stem cells, and then, into working neurons. This is only the second time of which I am aware that ES cells were made primarily into the kind of cells that scientists were aiming for. From the press release:UCLA's Yi Sun, an associate professor of psychiatry and biobehavioral sciences, and Howard Hughes Medical Institute investigator Thomas Sudhof at the University of Texas Southwestern Medical Center were able to produce 70 to 80 percent of neurons in cell culture. Sun and Sudhof 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.
Note that these cell lines are not being considered for therapeutic purposes and the press release does not say whether they came from "Bush-approved" lines.
Here's another interesting point that the media might miss: The scientists discovered that ES cells may not be pluripotent, that is, able to become any kind of cell. Rather, they might be predisposed to become cells from a certain lineage. Again, from the press release:
Pluripotency has been the gold standard supporting scientists' claim that ES cells offer the "best hope," for regenerative medical treatments. So far, that claim has been entirely theoretical. This research may indicate that the expected pluripotency of embryonic stem cells may not materialize.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.
Labels: ESCR. Pluripotency.
posted by Wesley J. Smith @ 8:44 AM
4 Comments
4 Comments:
Two errors. ES cells have been derived into multiple cell types not just two. Not every cell type makes it into the news however. Try reading the journal "Stem Cells" for specific examples. Off the top of my head I remember seeing pancreatic islet cells being purified at high efficiency in the last few months, derivation of hematopoietic stem cells, and germ cells. Even sperm and eggs have been derived from ES cells and used to make more animals. Our lab has purified smooth muscle from stem cells for instance.
Second, your definition of pluripotency is flawed, and this result is a common problem in stem cell science. The manipulation of cells in culture - any cells - makes it so that individually isolated clones aren't 100% identical. I don't know why they were surprised by this. Our group also has published on an experience related to this using embryonal carcinoma cells. We found one clone preferentially differentiated into smooth muscle compared to all other clones - even though parent line was thought to be pluripotent individual clones from the line showed variable efficacy. Interesting, but not new.
None of this changes the requirements of pluripotency, which ES cells have demonstrated over and over again. That is, they are capable of regenerating an entire embryo - every tissue. This has been shown with mouse tetraploid rescue studies in which the entire embryo is ES-cell derived. Just because some clones end up less than 100% pluripotent doesn't say anything about the cells as a whole. It just means the culture can have variable effects on cells.
Markh: Thanks for dropping by. That living human embryos eventually develop every tissue is self evident. It remains entirely theoretical in any other context, at least involving human cells. Indeed, it has not been done. It may never be done. It may be done. But it cannot be said scientifically that it can be done until it is done. To state that ES human cells are categorically pluripotent in the context of in vitro is not scientifically accurate without the modifier, "in theory."
Cloning is a different issue altogether. They have yet to be able to even derive human ES cells from cloned embryos. The experiment I posted on was not a cloning experiment.
That's a stretch. Every species, including non-human primates, that have had an ESC population derived have shown totipotency. The experiment that proves this is simply unethical to perform. Formation of an inner-cell mass that is responsible for the formation of every tissue in an embryo is a common feature across placental mammals, it would be rather extraordinary for humans to be the exception to the rule.
In vitro testing using embryoid body formation or aggregation is the next best thing and hES cells create tissues from all three embryonic layers just like other species' ESC lines do. There is no good reason to expect human ES cells to be different from those of other primates, rodents etc., just because of this result which is pretty typical of cell cloning. I am nonplussed.
I am non plussed that you would disagree with my statement that until it is actually done, as a matter of scientific accuracy, it can't be stated categorically. That is science how science works. I agree that in theory embryonic stem cells have that capacity. But that doesn't mean they actually have it outside of the living organism.
As once scientist stated about this very story: "In neither mouse or human ESCs has it been demonstrated that even the "220" cell types can be made in the laboratory. People simply believe this as a matter of faith, given that ESCs can are "pluripotent" in embryos."
It is more than faith, I believe. But certainly less than fact.
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