Cloned stem cells are indistinguishable from fertilized stem cells.

Skin cells are designed to form skin, not full-blown fetuses. So when scientists try to clone an animal by taking the nucleus of a skin cell and injecting it into an egg, the resulting animal is invariably freakish. As a result, most cloned animals die at or before birth. Those that live into adulthood almost always have serious health complications.

So, won’t embryonic stem cells taken from skin cell clones be abnormal as well? Is cloning therapy doomed to failure? Are patient-specific stem cells a pipe dream from the long lost glory days of Hwang Woo-suk?

Thankfully, no, says a paper out of the Whitehead Institute for Biomedical Research at MIT, published in the January 16th issue of Proceedings of the National Academy of Sciences. The MIT researchers proved that stem cells derived from cloned embryos are identical to those derived from normally-fertilized embryos.

“If fertilization-derived stem-cell lines are good, useful and safe for therapy, then cloned stem-cell lines should be just as safe and useful,” said postdoc Tobias Brambrink, the study’s lead author.

Brambrink said cloned animals fail to develop normally because of problems with gene expression—which genes are turned on and which are turned off. An adult skin cell, for example, is programmed so that its genes make the cell skin-like. When the skin cell nucleus is then injected into an egg, the egg must reprogram its newfound genome. This enables the egg to act as a versatile embryo, not as a fixed skin cell. This process goes awry for the vast majority of cells in a cloned embryo: The cloned cells retain traces of their skin-cell lineage, and the embryo fails to develop into a normal fetus.

To create a stem-cell line from a cloned egg, scientists fertilize the egg and let the resulting embryo develop for three and a half days, when it has formed a blastocyst of 60 to 120 cells. They then strip the blastocyst down to its inner cell mass and place this in a petri dish. Most of the cells die, but the few that survive multiply to create a stem-cell line. According to Brambrink’s data, this stem-cell line is perfectly normal.

Brambrink and his team examined five fertilized embryonic stem-cell lines and five cloned embryonic stem-cell lines, all from mice. They used an expression-profiling platform that allowed them to look at the expression levels of 30,000 specific genes in each cell line. They found no significant difference in expression between any of the lines. The cloned stem cells didn’t retain any traces of their roots; rather, they behaved like normal embryonic cells.

Prior to this experiment, there was already functional evidence that cloned embryonic stem cells behave just as normal ones, Brambrink said. Researchers had created normal mice from cloned embryonic stem cells by injecting stem cells into a blastocyst. However, Brambrink pointed out, this functional evidence didn’t rule out the possibility of gene expression abnormalities.

“The question was really: These functionally normal stem-cell lines—were they also molecularly normal?” Brambrink said. “And that is what this paper proves, that on the gene expression level, we don’t see any differences.” 

“Our data is a confirmation, but it’s also going beyond what we knew before.”

Originally published January 18, 2006

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