Additional problems cropped up in March, however, when New Scientist reported that a single image had appeared three different times in data from Verfaillie's lab—once referring to bone and once to cartilage in a 2001 Blood paper about human MAPCs, and once again to describe bone cells in a 2006 patent application.
In January, shortly before the first data problems came to light, Verfaillie's work had received a boost when her lab together with Weissman's reported they had replicated a second finding from the 2002 Nature paper—that MAPCs could partially replace the destroyed bone marrow (where red blood cells are manufactured) of mice, which by itself is unusual because they did not come from blood-forming stem cells, Weissman says. He adds, however, that if they work as reported, MAPCs are still not very efficient: one adult blood-forming stem cell replaced as much bone marrow as a million MAPCs.
"There's still a lot of skepticism about the paper, even though Irv is on it," says Chien. Weissman says his lab has still not created MAPCs. For the experiment with Verfaillie, who now heads stem cell research at the Catholic University of Leuven in Belgium, one of his current postdoctoral fellows, Scott Dylla, implanted the cells in mice in Leuven and brought them to Stanford to be examined.
Experts hesitate to pass judgment on Verfaillie, whom they describe as a careful researcher. Still, the fishy figures and lack of replication have raised eyebrows. "It all smells really bad," says stem cell biologist Sean Morrison of the University of Michigan at Ann Arbor Center for Stem Cell Biology. The important question, he says, is still whether the findings can be reproduced. "There's a tendency now for people to really tee off on Catherine" prematurely, he says. Verfaillie did not return phone calls or e-mails asking for comment.
Although opponents of embryonic stem cell research latched onto transdifferentiation and MAPCs, few scientists have ever proposed adult stem cells as an alternative to embryonic ones, Morrison says. Eva Mezey, a stem cell biologist at the National Institutes of Health who published one of the transdifferentiation studies and stands by the effect, notes that embryonic cells are naturally more versatile than adult stem cells. "That's their job," she says.
Morrison says the transdifferentiation studies have left a black mark on the field but represents only a subset of research. "There are always people with a get-rich-quick mentality," Morrison says. "It's an occupational hazard in any field where there's a possibility of having your paper end up on the front page of the New York Times. The fact that this is a high profile field means that when people make mistakes it gets more attention."
"Where all of this gets really risky," Caltech's Anderson adds, "is when clinicians start to move forward with trials that are based on experimental results that may not be solid."
Transdifferentiation studies spawned a number of clinical trials, including several in which heart attack patients received an injection of blood-forming stem cells in their hearts in hopes of replacing dead cardiac muscle. The results came in last year and were not encouraging: In two shorter trials, heart function improved by a few percentage points or not at all, and one longer study found a slight but temporary benefit.
Weissman says that most clinical studies of stem cells fail to meet what he sees as key criteria: They should be based on clear, peer-reviewed demonstrations of tissue regeneration, replicated by a large number of independent groups that provide rapid, long-lasting benefits.
Chien agrees that basic stem cell biology has not kept pace with clinical studies, but he says there is a compelling need for new treatments. "I can understand why people are motivated to try to do something" by conducting trials, he says. "They're going to go on and we will learn something from them," he notes, although he adds that treatments currently in the clinic are unlikely to enter the mainstream.