Induced Pluripotent Stem Cell Transplant Claims Debunked

When this report first appeared, it seemed too good to be true and it turns out it probably was. Nobel Laureate Shinya Yamanaka at Kyoto University announced his remarkable discovery of induced pluripotent stem (iPS) cells in 2006. However, another Japanese researcher, Hisashi Moriguchi, made an even more earth-shaking claim earlier this year. Moriguchi, who was a visiting researcher at the University of Tokyo, claimed to have modified iPS technology to treat a person with terminal heart failure. The patient was allegedly surgically treated in February, 2012, according to a front-page article in the Japanese newspaper Yomiuri Shimbun. The article also said that the patient was healthy. If this was true, this would certainly be an earth-shaking result. An unidentified head of a Tokyo-based organization devoted to helping children with heart problems, told Yomiuri Shimbun, “I hope this therapy is realized in Japan as soon as possible.”

The Nippon News Network had posted a video of Moriguchi presenting his research at the New York Stem Cell Foundation, but they have since removed this video.

Unfortunately, once the journal Nature was altered to this report, they contacted Harvard Medical School and Massachusetts General Hospital (MGH), where Moriguchi claimed to have performed this work. Both institutions denied that Moriguchi had even done such a procedure. According David Cameron, a spokesperson for Harvard Medical School, “No clinical trials related to Dr Moriguchi’s work have been approved by institutional review boards at either Harvard University or MGH.” Likewise, the public affairs officer for MGH, Ryan Donovan, said “The work he is reporting was not done at MGH.”

There are other problems with Moriguchi’s work. Moriguchi reported that he had invented a method to reprogram cells using just two chemicals: a small molecule that inhibits a small RNA called “microRNA-145” and another molecule that binds the TGF-β receptor. However, a University of Tokyo stem-cell researcher, Hiromitsu Nakauchi, said that he has never “heard of success with that method.” Nakauchi even said that before this week he had never heard of Moriguchi.

Another bizarre claim made by Moriguchi was that he could differentiate iPS cells into heart muscle cells by utilizing a ‘supercooling’ method that he had invented. Nakauchi said that this was “another weird thing.”

Moriguchi never published his technique in a peer-reviewed journal, but in a book about advances in stem-cell research (see Moriguchi, H., Mihara, M., Sato, C. & Chung, R. T. in Embryonic Stem Cells — Recent Advances in Pluripotent Stem Cell-Based Regenerative Medicine (ed. Atwood, C.) 359–370 (InTech, 2011)). In this book, there are paragraphs copied almost verbatim from other papers. For example, a section under the heading “2.3 Western blotting” is identical to a passage from a 2007 paper by Yamanaka (see Takahashi, K. et al. Cell 131, 861–872 (2007)). Furthermore, section 2.1.1 describes human liver biopsies but the information in this section matches the number of patients and timing of specimen extractions described in an earlier article, but the name of the institution has been changed (see Thenappan, A. et al. Hepatology 51, 1373–1382 (2010)).

Nature contacted Moriguchi and he stood by his publication. He told Nature, “We are all doing similar things so it makes sense that we’d use similar words.” However, he did admit to using other papers “as reference.”

With respect to his reported supercooling technique, Moriguchi cited a paper of his own in Scientific Reports, which is published by the Nature Publishing Group. Nature, however, noted that this paper describes supercooling of human ovaries for preservation (Moriguchi, H., Zhang, Y., Mihara, M. & Sato, C. Sci. Rep. 2, 537 (2012)). The paper has nothing to do with the differentiation of iPS cells into cardiac cells. Moriguchi said that a journal referee had recommended that he leave the latter experiment out of the paper “because it’s basically the same technology”.

Moriguchi said that he did most of the contentious work himself, including safety research in pigs. However, the initial surgery and some of a further five similar procedures in other patients that took place from August onwards, and while, according to Moriguchi, other researchers were supposedly involved in some of these procedures, he would not provide any names.

Where did Moriguchi acquire the surgical expertise to perform these procedures? Moriguchi initially told Nature that earned a medical degree at the Tokyo Medical and Dental University, and that he learned surgery there. However, in his later conversation with Nature, Moriguchi said that he has a nursing degree from the institution and not a medical degree.

The University of Tokyo confirmed that Moriguchi held a position there from 2006 to 2009, during which he studied “medical economics” and “evaluation of clinical technologies.” Currently, he is a visiting researcher at the university, working in the laboratory of Makoto Mihara in the university hospital’s cosmetic-surgery section, where, according to a secretary, he “comes in once or twice a week.”

Moriguchi also claimed to have a laboratory at MGH and Harvard Medical School, but these institutions only confirmed that Moriguchi was a visiting fellow at MGH in 1999–2000, but he has not been associated with the hospital or the medical school since then.

Nature asked Moriguchi who had funded his iPS cell procedures and where they had been carried out, where his ethical review had taken place and which good manufacturing practice (GMP) facility had produced the necessary clinical-grade iPS cells, Moriguchi referred again to MGH and Harvard Medical School, but he could not name the head of the ethical review board or any contacts at the GMP facility.

Jerome Ritz, co-director of the Connell O’Reilly Cell Manipulation Core Facility at Harvard Medical School, told Nature, “We have not produced any iPS cells for any patients in our facility. I can’t imagine what other facility might have produced these cells.”

What do we have? We have a Japanese researcher who is a liar and who has as much of a problem telling the truth as Barak Obama. This clinical trial clearly never happened and Moriguchi should be banned from further stem cell work.