"Flawed" Adult Progenitor Cells Study

Lots in the stem cell news about the report a few years ago that certain populations of adult stem cells can become "any cell in the body."

No one doubts whether Verfaillie found the stem cells that she said she did. The problem is that there were mistakes in the reports about how she actually did it and that other labs have had a hard time duplicating her work. From the New Scientist article on the "flaws":

"In her most recent paper, Verfaillie and Irving Weissman, a stem cell biologist at Stanford University in California, showed that MAPCs can give rise to all the cell types found in blood, but it is still unclear whether MAPCs are as versatile as she claimed in the original Nature paper."

Many researchers are unable even to isolate them. “They’re very testy cells,” observes Amy Wagers of Harvard University, who spent a week in Verfaillie’s lab trying in vain to learn the technique.

The problems with the marker profiles may help explain these difficulties. “If I had been following this recipe since 2002, I’d be extremely angry,” says Jeanne Loring, a stem cell biologist at the Burnham Institute for Medical Research in La Jolla, California.

There's a much more detailed evaluation on the original report in yesterday's The Scientist:

Tim Mulcahy, vice president for research at the University of Minnesota, told The Scientist that the university asked two experts in flow cytometry to review the data, and they found "technical flaws with the paper," but said they didn't have the background to determine if the problems affected the results. The university then contacted three stem cell experts, and two agreed to review the data. One reviewer said the flawed data wouldn't affect the findings, and the other said the flaws might "weaken the conclusions," Mulcahy noted. He said the university decided to release the information to allow the scientific community to debate the impact of the panel's findings. The university is not releasing the names of the stem cell experts who reviewed the data.

Mulcahy added that Verfaillie asked the university to investigate the findings, and has been very helpful. "This was all done with her consensus and her willing cooperation."

The outside experts agreed with Aldhous that the antigenic markers used to define the MAPCs were in question, Verfaillie said -- "as do I," she added. But these concerns don't affect the results, she noted. "As MAPCs were - and still are - not defined on the basis of a phenotype, but based on functional criteria, I believe therefore that the conclusions of the papers are still correct. Obviously that is up to the scientific community to decide."

The current debate is over a "minor point," said Diane Krause, a stem cell researcher at Yale University. The concerns about the Nature paper focus on the "antigenic profile of these cells, and not what they can do," she told The Scientist. "I certainly believe Catherine," Krause added. "I think she's got the highest amount of integrity."

Indeed, researcher Mark Clements, from Westminster University in London, UK, has had some success replicating Verfaillie's results with human cells. "The inaccuracies in Catherine's papers do cast a shadow over her work," he told The Scientist, "but I do believe the underlying premise is valid."

Clements said the errors in the paper raise questions about the definition of MAPCs in terms of cell markers, but agreed that the overall premise of the paper is intact. "Our experience of the human cells tells us that the main problem with them is that they're so fastidious to grow," he said. This would explain why other labs and indeed Catherine's lab have had difficulties replicating this work, Clements said.

Thomas Braun from the Max Planck Institute for Heart and Lung Research in Germany told The Scientist he thinks the explanation for the duplication of the figures was adequate. "Things like that happen although it is always hard to understand why such errors are not recognized at an earlier stage," he said.

A follow up study published in Journal of Experimental Medicine (I don't have link) and reported on in Science,that included doubter Irving Weissman proved multipotency, if not pleuripotency.

"The work has impressed one skeptic, Stanford blood stem cell researcher Irving Weissman, who collaborated on the new work. Weissman calls the result "remarkable." His skepticism, he adds, "makes me a perfect collaborator, because I insisted on very rigorous criteria for the experiments."

He emphasizes, as does Verfaillie, that these cells are clearly not as versatile as ES cells. But despite their limitations, they could prove to be useful therapeutically.

"A lot of people have lost interest in MAP cells by this point," says Weissman. "What our paper will help do is get everybody to look at it again." Others agree. "I'm sure it will revive interest in MAP cells," says stem cell researcher Paul Schiller of the University of Miami, Florida."

Perhaps, now that the "recipe" is corrected, more labs will confirm the original reports.

Different populations and kinds of adult stem cells are indeed very versatile, especially for producing what we really want: stable cells that will only become the exact specialized cells that are needed, where they are needed.

Adult stem cells have yielded more populations of specific progenitor and stem cells than even embryonic stem cells. The only place that embryonic stem cells work to produce "every cell in the body" is in the original container - in the intact embryo. Elsewhere, they produce embryoid bodies or teratomas, or mutate and die out unless first manipulated to become a more specialized stem cell or progenitor cell.

Which sounds like an adult stem cell or progenitor cell, to me.

Part of the problem with all stem cell research is that, as in the press coverage, scientists have also been "shotgunning" with groups of cells as though all samples stem cells are a bunch of homogeneous one size fits all entity. Slowly but surely, we're learning what markers to look for in order to find the most primitive or the exact future lineage we need, the environment, stimulating factors and the epigenetic factors involved.

If we think the progress has been fast before, I don't think it's anything like what will happen in the next 5 years.

(HT to FreeRepublic's neverdem.)