Groundbreaking research on stem cells presented by Haruko Obokata of the RIKEN Center for Developmental Biology has recently come under serious scientific scrutiny. Concerns about the research data and the reproducibility of the results have prompted Nature and the RIKEN Center to launch investigations into Obokata’s original work.
The research, published in two papers in the January 2014 edition of Nature, describes a seemingly simple technique that can convert mouse blood cells into embryonic stem cells through the use of an acidic solution. According to Obokata’s research, 25 minutes of an acid bath and a slight tweaking of the cellular culture can give rise to cells without a specific tissue fate. Obokata and her team dubbed these cells stimulus-triggered acquisition of pluripotency (STAP) cells.
The results of Obokata’s study inspired scientists across the globe to attempt duplication. Cells in an embryonic state are pluripotent, meaning they can give rise to any cell type in the body. Such degree of cellular potential makes these cells useful for studying disease development and drug efficacy. They may also prove useful for regenerative medicine, as further scientific developments may make it possible to repair or regrow organs from a single cell of the patient’s body.
Scientists were understandably excited after reading Obokata’s research and results. However, somewhat disconcertingly, no one outside of the study’s original group has successfully reproduced the STAP cell results.
Yoshiyuki Seki, a researcher at Kwansei Gakuin University’s School of Science and Technology in Japan, attempted to replicate Obokata’s method in mouse cells and failed. Seki is open to scientific amendment, thinking that there may be a necessary process not included in the original papers.
Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla, Calif., attempted duplication with human cells and failed. Teruhiko Wakayama, a researcher at Yamanaski University and a co-author of both of the original papers, says he also hasn’t been able to reproduce Obokata’s results since leaving the RIKEN Center.
Such frustrations reached a new level of concern when users on PubPeer, a forum dedicated to the discussion of published scientific results, highlighted problems with the images and data presentation in the Nature papers. In one of the papers, a lane in a genome analysis looks like it was retrospectively added. In the other paper, two images of placentas from different experiments appear to be the same.
While these image mistakes do not alter the results, they do generate anxiety over scientific sloppiness. In fact, this is not the first time Obokata’s research presentation has been questioned. A 2011 paper published by Obokata in Tissue Engineering includes a bar graph of stem cell markers that seems to have been inverted and reused later in the paper.
However, Obokata and her team are not the only ones at fault. In the publication of the two STAP cell papers, Nature bypassed its usual policy of presenting genomic data on a publicly accessible site. This extra transparency allows outside scientists to properly gauge the validity of scientific results. By overlooking this policy, Nature left curious and skeptical scientists in the dark.
Irrespective of the image debacle, the scientific inability to repeat Obokata’s experiment undermines some of the original hype surrounding the research. The STAP cell technique was presented as a simple method to induce pluripotency, thereby offering a more viable avenue to further stem cell research. These cells, despite their scientific potential, have been notoriously difficult to obtain. The government severely restricted the use of human embryos, a rich source of stem cells, for scientific research during the Bush administration. In 2006, Takahashi and Yamanaka appeared to make these restrictions obsolete by showing that four genes could switch differentiated cells into induced pluripotent stem cells. However, the techniques of Takahashi and Yamanaka are difficult to perform, leaving stem cells as the limiting factor in research. The scientific world, exposing its desperation, drew a premature breath of fresh air with Obokata’s results.
