Whitehead Institute researchers have found that human embryonic stem (ES) cells and adult cells reprogrammed to an embryonic stem cell-like state exhibit very few differences

CAMBRIDGE, Mass. (August 5, 2010) – Human embryonic stem (ES) cells and adult cells reprogrammed to an embryonic stem cell-like state—so-called induced pluripotent stem or iPS cells—exhibit very few differences in their gene expression signatures and are nearly indistinguishable in their chromatin state, according to Whitehead Institute researchers.
Their results are published in the August 6 issue of Cell Stem Cell.
iPS cells are made by introducing three key genes into adult cells. These reprogramming factors push the cells from a mature state to a more flexible embryonic stem cell-like state. Like ES cells, iPS cells can then, in theory, be coaxed to mature into almost any type of cell in the body. Unlike ES cells, iPS cells taken from a patient are not likely to be rejected by that patient's immune system. This difference overcomes a major hurdle in regenerative medicine.
"Billions of dollars have been invested in the idea that we will use ES cells at some point in the future as therapeutic or regenerative agents, but for ethical and practical issues, this may not be possible," says Garrett Frampton, a co-first author on the Cell Stem Cell paper and a graduate student in the lab of Whitehead Member Richard Young. "But if they work out therapies with ES cells, and iPS cells are equivalent to ES cells, then the idea is that those therapies could be used with iPS cells as well. Whereas if iPS cells are different from ES cells, then who knows if you can use iPS cells for therapy?"
Since iPS cells were first developed in 2006, the similarities and differences between ES and iPS cells have been hotly debated in the scientific community. Thus far, researchers have gauged the cells' equivalence by determining whether the cells express the same genes, but such studies have yielded mixed results.
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"At this stage, we can't yet prove that they are absolutely identical, but the available technology doesn't reveal differences," says Young, who is also a biology professor at MIT. "It does mean that iPS cells could be useful as personal ES cells in the future."
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"The key question is, are any of these differences functionally relevant? Do they change how a cell matures or not?" says Whitehead Member Rudolf Jaenisch, whose lab worked closely with Guenther and Frampton. "The earlier documented differences were more noise than anything. But other tests may give you a different answer. So it is still an open question, something that the field will continue to struggle with and have to decide."
Guenther agrees.
"Our paper addresses the ground state of iPS and ES cells in a laboratory setting," he says. "But we don't know for a fact that they won't behave differently when they mature into various cell types or tissues. That's the next step."
Source-Eurekalert