It's certainly a logical assumption that if you can't get embryonic stem cells, adult stem cells - which also retain the capacity to divide and form different cell types, though to a lesser degree than embryonic stem cells - are the next best thing in terms of producing a variety of different cell types.

But a paper in the October 2006 issue of Nature Genetics suggested that, logical or no, as far as cloning is concerned, the assumption is false.

The paper underscored just how far cloning, despite all the hopes pinned on it, is from being a weapon in the clinician's arsenal. Cloning with the sort of efficiency that is necessary for a reliable clinical procedure "has never been practical - never," Tao Cheng told BioWorld Today.

"Given the lesson we learned in the past year, with some hype in the field, we advocate back to the basics," added Cheng, who is the paper's co-senior author.

The "hype" Cheng delicately referred to was arguably science's most spectacular flameout of 2005: the discovery that Seoul National University's Woo-Suk Hwang had fabricated data to support his claim that he had created patient-specific stem cell lines with high efficiency, and had created embryonic stem cell lines by taking the nucleus of a woman's cell and transferring it into one of her own oocytes. (See BioWorld Today, Jan. 11, 2006.)

But cloning and stem cell research remain hot areas. The new findings challenge the conventional wisdom about cloning, casting doubt on the therapeutic utility of adult stem cells, but also suggesting that cloning might not need stem cells at all.

In the Nature Genetics paper, researchers from the University of Connecticut in Storrs, the University of Pittsburgh in Pennsylvania, and Yale University in New Haven, Conn., reported on comparing cloning success rates when using an adult blood-forming stem cell and its daughter cells. They compared the stem cells to progenitor cells, which can no longer become all types of blood cells but still give rise to several different cell types, and fully differentiated blood cells called granulocytes, which no longer divide.

When the researchers isolated nuclei from each of those cell types and transferred them to unfertilized eggs, the rank order was pretty much the opposite of what one might predict: Granulocytes were the most successful, with roughly a third of cells making it to the stage of an early embryo, or blastocyst. (Embryonic stem cell lines can be generated from embryos once they have reached the blastocyst stage.) In second place were progenitor cells with a success rate of about 10 percent, with the hematopoietic stem cells coming in a solid third at a success rate of 4 percent.

The findings "again reinforce the notion that adult stem cells are fundamentally different from embryonic stem cells," Cheng said, adding that the current weight of the evidence suggests that "their developmental potential is very, very limited."

The findings also suggested that embryonic stem cells, which present ethical challenges - and on the practical level, regulatory ones, as well - might not be irreplaceable in the quest for therapeutic cloning. The researchers also cloned with embryonic stem cells as a control, and had a success rate of about 50 percent blastocyst formation in those experiments, as opposed to roughly 35 percent to 40 percent blastocyst formation when using differentiated granulocytes. Past the blastocyst stage, the data favored embryonic stem cells more strongly: 18 mouse pups were born from cloned embryonic stem cells, while granulocyte cloning gave only two pups, both of which were extremely short-lived. But the data as a whole nevertheless suggested that Dolly the sheep, and animals cloned since, were indeed cloned from fully differentiated cells, not from adult stem cells as some researchers have suggested.

Cheng said that he is interested in cloned cells as a model system, calling it "a very powerful tool" for basic insights into cell division and cancer biology. But as for therapeutic cloning, he thinks that it's going to be a long and winding road: "If we don't even know what type of cell can be used for nuclear transfer, how can we talk about therapeutic cloning tomorrow?"

No Comments