It has been a crazy week for stem cell research. After the high of a Nobel prize for Japan’s Shinya Yamanaka, the pioneer of cellular reprogramming, events took an alarming and surreal turn when a little-known compatriot – Hisashi Moriguchi – claimed to have already run a clinical trial in which similarly reprogrammed cells were injected into people.
But Moriguchi’s claims quickly unravelled. “I have not found a single person to say anything concrete indicating that this has really happened,” says , a stem cell researcher at the University of California, Davis, who .
In a poster presented at a , Moriguchi – who claimed to work at Harvard Medical School and the University of Tokyo – described results from a trial in which cardiac muscle cells were grown from induced pluripotent stem (iPS) cells, and transplanted into six US patients with severe heart failure.
The Yomiuri Shimbun newspaper – Japan’s biggest – splashed the story, based on an interview with Moriguchi, who claimed he had received ethical approval from (IRB).
Advertisement
This was surprising, given the safety concerns that surround iPS cells – adult cells that have been reprogrammed to an embryonic state. Support for the claim quickly disintegrated: within hours, Harvard released a statement noting that Moriguchi had no current affiliation with the university, nor any ethical approval to run a clinical trial.
Moriguchi’s poster describing the clinical trial was taken down after the New York Stem Cell Foundation learned of Harvard’s statement – but a . This suggested an improvement of 41.5 per cent in “” – a measure of heart output – in patients whose hearts were injected with iPS-derived cells, compared to 4.1 per cent in a placebo group.
That would have been an astonishing claim, says at the University of Washington in Seattle, who is working to develop cell therapies for heart attack: “I’m not aware of any clinical trial that reported anything of this magnitude.”
Indeed, similar studies involving adult stem cells have typically found improvements of less than 5 per cent ().
Moriguchi did not respond to emails from Â鶹´«Ã½. But on Saturday that for five of the patients he was actually describing “planned” procedures. Still, Moriguchi maintained that he had transplanted cells into one patient at an unidentified hospital in Boston.
Â鶹´«Ã½‘s enquiries raise further questions about Moriguchi’s work. In papers published earlier this year, he described experiments on freezing human ovarian tissue (), and a remarkable claim to be able to eliminate liver tumour cells using a reprogramming technique (). Both gave Harvard and University of Tokyo affiliations, and claimed ethical approval from each institution.
Affiliation questions
The University of Tokyo that Moriguchi was a visiting researcher in the cosmetic surgery department.
According to Harvard, Moriguchi has not worked there since a brief appointment as a visiting fellow at the Massachusetts General Hospital, which is affiliated with Harvard Medical School, from 1999 to 2000.
The Nature Publishing Group, which publishes Scientific Reports, says it is now “investigating the issues that have arisen around academic affiliation and IRB approval”.
In 2010, Moriguchi claimed to have invented a method to create iPS cells using just two chemicals, rather than a combination of genetic factors, as used by Yamanaka and others. This bold claim was made in a short correspondence (), rather than a full paper – and has never been verified.
“I know of no lab, despite huge efforts worldwide, that has yet succeeded in deriving iPS cells with chemicals alone,” says of the Children’s Hospital Boston.
Veracity doubts
of the Massachusetts General Hospital, who advised Moriguchi on preparing that note and is named as a co-author, said in a statement issued through the hospital that he is “no longer confident in Dr Moriguchi’s veracity”. The statement added that Chung was unaware until this week that Moriguchi had also listed him as co-author of a .
Chifumi Sato of Tokyo Medical and Dental University, the other author on the Hepatology correspondence, says that Moriguchi had told him that he was working in the US with Chung and other collaborators.
Meanwhile, Nature‘s news blog that two images in Moriguchi’s publications, purportedly illustrating his own work, seem remarkably similar to images on the website of the Advanced Fertility Center of Chicago, and from a paper by Yamanaka.
In the light of the fallout from its story, the Yomiuri Shimbun has published a , and has promised an in-house investigation.
Given concerns that iPS-derived cells may be prone to becoming cancerous, Knoepfler says that the best outcome would be if the entire story is a fantasy. “I really hope Moriguchi did not do these transplants,” he says. “That would be really disturbing.”
Topics:
