STAP cell

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STAP cells ( English stimulus-triggered acquisition of pluripotency , dt. "Stimulus-triggered acquisition of pluripotency ") were supposedly pluripotent stem cells (iPS) induced by simple external stimuli . In January 2014, two experimental papers appeared in Nature , in which lead author Haruko Obokata from the RIKEN Center for Developmental Biology and senior author Charles Vacanti claimed to have brought about such a conversion of somatic cells into stem cells through simple external stimuli. The results were artifacts . The work was therefore withdrawn in July 2014. A forensic investigation, published in Nature in September 2015 together with the report on further unsuccessful replication attempts , found that several “contamination events” of the alleged cell material with ordinary embryonic stem cells led to the results, which is difficult to explain as a mere oversight, see Fraud and forgery in science .

Information provided by the researchers

The STAP cells were produced by briefly lowering the pH value in the culture medium with hydrochloric acid (by diluting it to the pH level of citric acid ), by adding a weak bacterial toxin or by gently pressing. About 25% of the cells survived the treatment, of which about 30% were converted to Oct-4 -positive STAP cells . The lowering of the pH value leads, among other things, to stress for the cells, which is partly responsible for the change in the cells. The method for generating the STAP cells was developed by Obokata at Brigham and Women's Hospital (BWH) in Charles Vacanti's group and then optimized at the RIKEN Center for Developmental Biology. In 2008, Obokata tested methods of reprogramming through cell stress at Harvard Medical School for Vacanti, including forcing cells through microcapillaries . The first attempts at dedifferentiating cell types to STAP cells were achieved with leukocytes , then nerve , skin and muscle cells were examined. In February 2014 Vacanti declared that the method also works with human cells.

Examination of the research results, consequences and consequences of the affair

Since the technique could represent a significant simplification for the generation of induced pluripotent stem cells, various research groups attempted to reproduce the results . After various groups were unable to reproduce the results, doubts about the accuracy of the publication were expressed. Obokata's employer RIKEN opened an investigation on February 15, 2014. Nature also announced an investigation. Some stem cell researchers defended Obokata or reserved judgment while the investigation was ongoing. To address the reproducibility problem, on March 5, Obokata published some technical advice on the procedural protocols used. On March 11, 2014, Teruhiko Wakayama asked his co-authors to withdraw the publication. Vacanti objected to the request and published details of the method on its website.

The RIKEN investigation was intended to clarify six points of criticism. These included a presumably edited picture of the genetic changes, a methodological section of text copied from her publications, an incomplete description of the method and a picture reused from her dissertation in a different context. Four of the criticisms were dropped. A reuse of a photo in a different context from her dissertation three years ago and an inadequate dating of her laboratory records were found. RIKEN assigned the inconsistencies to Haruko Obokata on April 1st. Obokata replied to the report that she was "amazed and upset" by the report, pointing out that the inconsistencies were not intentional. RIKEN also initiated an internal investigation into the reproducibility of STAP cell generation. The two publications were withdrawn from the journal Nature on July 2, 2014 . Obokata consented to the withdrawal of the two publications. In November 2015, Obokata was stripped of his doctorate.

A Nature article analyzing the controversy concluded that the reviewers of the manuscripts could not have clearly identified the problems before they were accepted. In the wake of the controversy, observers, journalists and former members of RIKEN have stated that the organization is imbued with unprofessional and inadequate scientific rigor and consistency, and that this reflects serious problems with scientific research in Japan in general. On August 4, 2014, Yoshiki Sasai , co-author of the controversial publication and manager of Obokata, committed suicide in connection with the STAP affair. The RIKEN assigned him the main culprit for the scandal because he had not adequately fulfilled his obligation to review as a reviewer and co-author.

literature

  • Kim Baumann: Stem cells: Reprogramming with low pH . In: Nature Reviews Molecular Cell Biology . 15, No. 3, 2014, ISSN  1471-0072 , pp. 149-149. doi : 10.1038 / nrm3754 .

Web links

Individual evidence

  1. ↑ a b H. Obokata, T. Wakayama, Y. Sasai, K. Kojima, MP Vacanti, H. Niwa, M. Yamato, CA Vacanti: Stimulus-triggered fate conversion of somatic cells into pluripotency. In: Nature. Volume 505, Number 7485, January 2014, pp. 641-647, ISSN  1476-4687 . doi : 10.1038 / nature12968 . PMID 24476887 .
  2. ↑ H. Obokata, Y. Sasai, H. Niwa, M. Kadota, M. Andrabi, N. Takata, M. Tokoro, Y. Terashita, S. Yonemura, CA Vacanti, T. Wakayama: Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. In: Nature. Volume 505, Number 7485, January 2014, pp. 676-680, ISSN  1476-4687 . doi : 10.1038 / nature12969 . PMID 24476891 .
  3. ↑ David Cyranoski (Nature): Papers on 'stress-induced' stem cells are retracted - High-profile reports claiming an easy way to create pluripotent cells were flawed, Nature announces . Nature breaking news, July 2, 2014.
  4. ↑ Daijiro Konno et al .: STAP cells are derived from ES cells . Nature 525, 2015, E4-E5, doi : 10.1038 / nature15366 .
  5. ↑ Alejandro De Los Angeles et al .: Failure to replicate the STAP cell phenomenon . Nature 525, 2015, E6-E9, doi : 10.1038 / nature15513 .
  6. ↑ David Cyranoski: Failed replications put STAP stem-cell claims to rest . Nature News, September 23, 2015.
  7. ↑ a b David Cyranoski: Acid bath offers easy path to stem cells . In: Nature News , Nature Publishing Group, January 29, 2014. Retrieved January 30, 2014. 
  8. ↑ James Gallagher: Stem cell 'major discovery' claimed . In: BBC News , January 29, 2014. Retrieved January 31, 2014. 
  9. ↑ Ian Sample: Simple way to make stem cells in half an hour hailed as major discovery . In: The Guardian , January 29, 2014. Retrieved January 31, 2014. 
  10. ↑ Steve Connor: Exclusive: The miracle cure - scientists turn human skin into stem cells . independent.co.uk. February 9, 2014. Retrieved February 9, 2014.
  11. ↑ a b RIKEN panel puts all the blame on Obokata ( Memento of the original from April 4, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . In: Japan News . Retrieved April 4, 2014. @1@ 2Template: Webachiv / IABot / the-japan-news.com
  12. ↑ David Cyranoski: Acid-bath stem-cell study under investigation. In: Nature. 2014, doi : 10.1038 / nature.2014.14738 .
  13. ↑ Haruko Obokata, Yoshiki Sasai and Hitoshi Niwa (March 2014). Essential technical tips for STAP cell conversion culture from somatic cells . Nature Protocols Discussion Forum.
  14. ↑ Prof. wants STAP findings withdrawn . In: The Yomiuri Shimbun , March 11, 2014. Archived from the original on March 17, 2014 Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . Retrieved March 17, 2014. @1@ 2Template: Webachiv / IABot / www.the-japan-news.com 
  15. ↑ Charles A Vacanti (2014) PROTOCOL FOR GENERATING STAP CELLS FROM MATURE SOMATIC CELLS ( Memento of the original from June 29, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . Center for Tissue Engineering & Regenerative Medicine. PDF ( Memento of the original from March 22, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . @1@ 2Template: Webachiv / IABot / research.bwhanesthesia.org @1@ 2Template: Webachiv / IABot / research.bwhanesthesia.org
  16. ↑ Review of Obokata stress reprogramming Nature papers. Knoepfler Lab Stem Cell Blog.
  17. ^ T. Bond: STAP cells: stress-induced stem cells? In: Regenerative medicine. Volume 9, Number 2, March 2014, pp. 133-134, ISSN  1746-076X . doi : 10.2217 / rme.14.12 . PMID 24750053 .
  18. ↑ Haruko Obokata, Who Claimed Stem Cell Breakthrough, Found Guilty of Scientific Misconduct . In: Newsweek . Retrieved April 4, 2014.
  19. ↑ Masaaki Kameda: Obokata falsified data in STAP papers: probe . In: The Japan Times , April 1, 2014. Retrieved April 2, 2014. 
  20. ↑ Press Release: Report on STAP Cell Research Paper Investigation . RIKEN. April 1, 2014. Retrieved June 2, 2014.
  21. ↑ Elaine Lies: Japan researcher agrees to withdraw disputed stem cell paper . In: Reuters , June 4, 2014. 
  22. ↑ H. Obokata, T. Wakayama, Y. Sasai, K. Kojima, MP Vacanti, H. Niwa, M. Yamato, CA Vacanti: Retraction: Stimulus-triggered fate conversion of somatic cells into pluripotency. In: Nature. Volume 511, Number 7507, July 2014, p. 112, ISSN  1476-4687 . doi : 10.1038 / nature13598 . PMID 24990753 .
  23. ↑ H. Obokata, Y. Sasai, H. Niwa, M. Kadota, M. Andrabi, N. Takata, M. Tokoro, Y. Terashita, S. Yonemura, CA Vacanti, T. Wakayama: Retraction: Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. In: Nature. Volume 511, Number 7507, July 2014, p. 112, ISSN  1476-4687 . doi : 10.1038 / nature13599 . PMID 24990752 .
  24. ↑ Nicoletta Charolidi: Stem-cell scientist loose doctorate over STAP controversy . Retrieved December 6, 2015.
  25. ↑ David Cyranoski: Research integrity: Cell-induced stress . Retrieved August 5, 2014.
  26. ↑ Otake, Tomoko: 'STAPgate' shows Japan must get back to basics in science. In: Japan Times , April 21, 2014
  27. ^ Schreiber, Mark, Ongoing Obokata story seeks out scandal. In: Japan Times , 5 July 2014, p. 19th
  28. ↑ Staff Report: STAP paper co-author Sasai commits suicide. In: Japan Times , August 5, 2014.
  29. ↑ DIE WELT: Stem cell researcher commits suicide after research scandal , August 6, 2014, accessed on December 6, 2015.