Two stem cell lines lead studies

In a decade of research on human embryonic stem cells (hESCs), scientists have largely depended on just two cell lines, greatly limiting the diversity of research in the budding field, according to a linkurl:survey published;http://bert.lib.indiana.edu:2146/nbt/journal/v27/n8/full/nbt0809-696.html in the August issue of Nature Biotechnology.

Human embryonic stem cells
Image: Wikimedia commons/PLoS
Nissim Benvenisty

"It's been sort of common lore that those [two lines] have been the most widely used," said bioethicist linkurl:Rob Streiffer;http://philosophy.wisc.edu/streiffer/ of the University of Wisconsin-Madison, who was not involved in the report, "[but] I was surprised that it was as lopsided as they found it to be." The embryonic stem cell policy implemented by former US president George Bush identified 64 lines eligible for federal funding; those lines were derived before August 9, 2001, from embryos left over from infertility treatments and donated with informed consent. Of those 64 lines, however, only 21 were actually available for distribution. And according to the new report, two lines of those 21 -- H1 and H9 -- have dominated the field for the past decade, severely limiting the diversity of hESC research. Analyzing cell line shipments from the National Stem Cell Bank (NSCB) and the Harvard Stem Cell Institute (HSCI) -- two of the largest US repositories of stem cells -- as well as 534 peer-reviewed publications using hESC lines, linkurl:Christopher Scott,;http://med.stanford.edu/profiles/Christopher_Scott/ director of Stanford University's Program on Stem Cells in Society, and his colleagues determined that H1 and H9 comprised the vast majority of hESC research. These two lines, derived by linkurl:James Thomson;http://discovery.wisc.edu/home/morgridge/research/regenerative-biology/ of the University of Wisconsin-Madison, accounted for more than 75% of hESC requests from scientists received by the NSCB in the last 10 years and were used in 60.9% and 83.3% of the published literature on hESCs, respectively. "Scientifically, this is not right," said molecular biologist Xiangru Xu of linkurl:Yale University,;http://www.yale.edu/ who did not participate in the research. "[These two lines] are well characterized but that doesn't necessarily mean that [they] are the best model for everything. Some of the [other] lines might be more suitable for different [types] of studies." Furthermore, "a lot of simple experiments require comparisons, and they require comparisons of more than two or three lines," added Mahendra Rao, vice president for research at linkurl:Invitrogen,;http://www.invitrogen.com/site/us/en/home.html a California-based biotechnology company, who was not involved in the survey. "Many experiments would benefit from having been done with a larger number of lines." Since 2001, more than 600 new hESC lines have been developed, but because they were ineligible for funding under the Bush policy, they have not made significant contributions to the literature. "New lines that were better were essentially frozen out," said Rao. "I'm sure they would have been used much more robustly had federal funding been available for them," Streiffer said. Policy limitations aren't solely responsible for the lack of cell line diversity, though; factors such as scientific inertia also played a role. Once the H1 and H9 lines were recognized as successful, working cell lines, more and more researchers began to use them. "If you use other lines," Xu explained, "you have to spend more time, more effort, [and] more money to characterize the very basic features of those lines." It was simply easier and more efficient to stick with what was already established, he said. The new stem cell guidelines issued by the Obama administration last month may offer an opportunity to boost the number of well-characterized lines. The new policy allows newly derived lines to be included in a soon-to-be-created registry of federally fundable lines. Lines created after July 6, 2009, must meet strict regulations regarding the embryo procurement process, and lines developed before that date will be reviewed on a case-by-case basis by a working group to be established by the NIH to ensure that they were derived ethically. "Having a number of lines that scientists can pick from is a good thing," said Scott. "It's something that the field wished that it had had eight years ago and didn't." It is important to branch out from the two lines that have been used so commonly, Xu added, and "to determine which lines are best for researchers to reach their different goals." The silver lining is, of course, the fact that scientists now "know pretty much everything about those two lines," Xu said. They have become an "encyclopedic standard against which new lines can be compared," Scott agreed.
**__Related stories:__***linkurl:NIH loosens stem cell consent rules;http://www.the-scientist.com/blog/display/55814/
[6th July 2009]*linkurl: Will new ESC rules hurt research?;http://www.the-scientist.com/blog/display/55692/
[14th May 2009]*linkurl: Policies stymie stem cell progress;http://www.the-scientist.com/blog/display/54727/
[4th June 2008]