Breakthrough Stem Cell Results Called Into Question

"Patients treated with iPS cells: Harvard University team injects cardiac muscle cells into 6 people," read a 12 October headline in the English edition of a prominent Japanese newspaper. The article went on to proclaim this "the first clinical application of iPS cells" and said the results were being presented at a conference in New York.

The claim, attributed in the news to Japanese researcher Hisashi Moriguchi, was quickly called into question by both Harvard University and the supposedly affiliated Japanese institutions.

Harvard communications officer B. D. Colen told Science this morning that Moriguchi was a visiting fellow at Massachusetts General Hospital (MGH) in Boston "from late November through the end of December of 1999." He "has not been associated with MGH or Harvard" since that time, Colen said. A Harvard statement added that "no clinical trials related to Dr. Moriguchi's work have been approved by institutional review boards at either Harvard University or MGH."

In Tokyo, meanwhile, a spokesperson for the University of Tokyo Hospital confirmed in a phone interview that Moriguchi is on staff as a project researcher, but emphasized that the work apparently reported in New York was not carried out in the hospital's labs.

The New York conference was held at Rockefeller University on 10 and 11 October, an annual gathering to discuss translational stem cell research sponsored by The New York Stem Cell Foundation. There, a poster by Moriguchi that detailed his cardiac study was taken down "before the second day of the conference," said David McKeon, chief of staff for the foundation. Susan L. Solomon and Kevin Eggan, the chief executive officer and chief scientific officer at the foundation, respectively, said in a statement that "the foundation has received information from Harvard University that raises legitimate questions concerning a poster presentation by Hisashi Moriguchi of The University of Tokyo. … In any instance where the foundation has questions regarding the research presented, it reserves the right to withdraw display and presentation of an abstract, and has done so in this instance." McKeon said he could not provide an abstract of the paper.

Stories published Thursday in the print edition of the Japanese Yomiuri Shimbun and Friday in the print English language The Daily Yomiuri about the research were removed from the Yomiuri Web site after questions were raised. The stories had described in detail how Moriguchi and colleagues injected induced pluripotent stem (iPS) cells into six patients with serious heart failure. The study would mark the first clinical test of the cells. iPS cells are mature cells that have been reprogrammed to behave more like cells from an early embryo. On Monday, iPS cell work was awarded the Nobel Prize in medicine or physiology. Japanese researcher Shinya Yamanaka was one of two honorees.

A publication search of Moriguchi's writings revealed that he has listed a Harvard affiliation, along with a position at the University of Tokyo Hospital, on several previously published papers and correspondence. Those include two papers published this year in Scientific Reports and correspondence published in 2010 in the journal Hepatology.

Furthermore, there is concern in Tokyo about some of the published work. The university hospital spokesperson says it is checking into two papers published this year in Scientific Reports. One paper describes cryopreservation of human ovarian cortex tissues. The authors state that: "The study was approved by the Institutional Review Boards of our institutions … and informed written consent was obtained from the patient." The Institutional Review Boards in question would include those at Harvard Medical School, the University of Tokyo, and Tokyo Medical and Dental University (TMDU). Tokyo University Hospital today determined that this work was not reviewed by its ethics committee but was still trying to confirm it had not been presented to one of the university's other review boards. "There is a lot that is unclear," said the hospital spokesperson, who, following common Japanese practice, asked to not be identified by name.

Investigations are also getting underway at TMDU. Moriguchi earned his undergraduate degree there and has co-authored numerous papers over the years with Chifumi Sato, whose research focuses on liver diseases and health promotion. At a press conference at the school Friday evening, Sato said he had agreed to be listed as a co-author on the poster presented in New York after Moriguchi sent him an abstract. A follow up fax sent to reporters later explained that Sato had specifically asked Moriguchi about approval by the Harvard review board and why the abstract did not include the names of any Harvard researchers. Moriguchi replied that "there was no problem," according to the fax. Sato said he assumed he would see a paper with more details before it was submitted to a journal. He said he learned there were questions about the work by reading the newspapers at home Friday morning.

Ikuo Morita, a university trustee who oversees research, said the school will set up a committee to investigate the validity of all Moriguchi's papers with a connection to TMDU. Sato said he would reflect upon his responsibilities as a co-author.

In early 2009, Moriguchi and Sato published a letter in Nature, responding to a news story on Japan's work in iPS cells. They expressed concern that Japan "is in danger of being overtaken in the field of human iPS-cell research" because of government regulations.

Moriguchi did not reply to an e-mail. A call to the newspaper Yomiuri Shimbun seeking comment was not returned.