Boston Blog

Stem cell research gets messy on Longwood Avenue

The first hit from a Yahoo search on “lung stem cells” this morning turned up a Boston Globe story on this week’s paper out of Brigham and Women’s Hospital. Played inside the paper, the story’s headline reads “Study finds lung stem cells, likely to generate debate.” It then goes on to detail how the findings, published in the New England Journal of Medicine, are likely to “generate skepticism within the field.”

The second hit takes you to the NEJM blog with the headline “Human lung stem cells: A breathtaking discovery?” Note the question mark.

Why all the qualifications? Pull that string and it gets very tangled as it winds its way back to two researchers who now work around the corner from each other on Boston’s Longwood Avenue. Amy Wagers, who in 2001 challenged co-author Piero Anversa’s earlier findings while she was at Stanford, now works at the Joslin Diabetes Center. And, while Wagers work raised questions about Anversa’s research, it turns out she’s dealing with some questions about her own work.

First, back to today’s reports. An NEJM editorial by Dr. Harold Chapman at the University of California, San Francisco that ran with the paper notes: It may be possible to bioengineer lung tissue that can help treat patients with lung injury. Using lung stem cells would avoid the many potential complications associated with allogeneic transplantation.

But, he qualifies the statement:

Kajstura et al report no evidence that the observed respiratory units integrate sufficiently with the host vasculature or airways to support perfusion or ventilation. There are reasons to anticipate such connections will develop, but can these stem cells efficiently assemble into a permanent, fully functional unit?

On the NEJM blog, Deputy Editor Dan L. Longo, M.D. rattles off a list of his own questions about the findings. If so much remains unanswered, why give it a marquee spot in the NEJM? As Longo puts it: The findings are intriguing and open new avenues of investigation.

The Globe also qualifies the finding by noting that work by co-author Piero Anversa has raised questions before.

Anversa’s work has fired vigorous debate among stem cell scientists before. A paper from his lab in 2001 found that bone marrow stem cells could transdifferentiate, giving rise to cells that could repair the heart. That work has been controversial, with some scientists disputing the validity of the findings."

Other Boston researchers quoted in the story were keen to point this out in the Globe. Dr. Kenneth Chien, a stem cell biologist Harvard Stem Cell Institute called the paper’s conclusions “daring” and noted that the researchers’ technology" has “limitations,” which have made it difficult for others to verify the group’s past findings.

A 2004 Newsweek story offers some details:

In 2001, news that adult bone-marrow stem cells had become cardiac muscle in mice spurred great hope, even leading to clinical trials in humans. Dr. Piero Anversa, of New York Medical College, worked on the original research and stands by it “1,000 percent.” But in April two groups reported that they could not reproduce the finding, a critical step in the validation of science. “Our paper says it doesn’t work,” says Stanford University’s Dr. Irv Weissman."

Which takes us back to Wagers. A 2008 story in The Scientist noted her role in the disputing Anversa’s earlier findings when she was a post doc in Weissman’s lab.: Wagers, the story stated, has: “reputation for putting other people’s findings to the test.”

However, the story also reported that, in 2007," Anversa at Harvard Medical School showed “unequivocally” that bone marrow stem cells could transdifferentiate to cardiomyogenic cells (Proc Natl Acad Sci, 104:17783-8, 2007). Anversa says the discrepancy is likely due to different methodologies…"

In the meantime both Wagers and Aversa ended up at Harvard research centers.

Just last summer, Wagers stood by her findings in a Q. & A. published in the journal Biotechniques. Here is her response to the question “what has been your most significant contribution to your field so far?”

When I began my position as a postdoctoral fellow in Irv Weissman’s lab at Stanford, there was a lot of enthusiasm surrounding the idea that hematopoietic stem cells in the bone marrow might spontaneously transdifferentiate to produce non-blood tissues. I rigorously tested this idea and found such activity to be negligible, if present at all. That changed the course of investigation by shifting the emphasis towards defining endogenous tissue progenitor cells that carry out regenerative functions.

Then, last year, Wagers work came under review. This from The Scientist. Find more on “”http://retractionwatch.wordpress.com/2010/10/14/highly-cited-harvard-stem-cell-scientist-retracts-nature-paper/“>Retraction Watch.”

A rising stem cell star has retracted a recent high-profile paper because of “serious concerns” with the data. A second paper in Blood by the same group is also under review.

Whether the retraction is due to a mistake or misconduct remains unclear, but a comparison of the papers done by Nature reporters found two sets of flow cytometry plots that seem to be duplicates.

Amy Wagers, a stem cell biologist at the Joslin Diabetes Center and assistant professor at Harvard Medical School, published a retraction with two co-authors on Wednesday (October 13) of a January 2010 Nature paper, cited 13 times, which found that factors in the blood of young mice can rejuvenate blood stem cells in older mice.

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