224:
engaged in "research misconduct", falsifying data on two occasions. The co-authors were cleared of misconduct, but bore "grave responsibility" for not verifying the data themselves. RIKEN also announced that an internal group had been established to verify whether the ‘stimulus-triggered acquisition of pluripotency’ is reproducible. Obokata maintained her innocence and said she would appeal the decision. On June 4, 2014, Obokata agreed to retract both the article and the "letter". The article was officially retracted on July 2, 2014. An article analyzing the controversy concluded that while issues of image manipulation, duplication and plagiarism were potentially detectable, the reviewers could not have concluded that the article was the product of academic misconduct prior to acceptance.
106:. On average only 25% of cells survived the acid treatment, but over 50% of those that survived converted to Oct4-GFPCD45 pluripotent cells. The researchers also claimed that treatment with bacterial toxins or physical stress were conducive to the acquisition of pluripotent markers. STAP cells injected into mouse embryos grew into a variety of tissues and organs found throughout the body. According to the researchers, the
236:, was discovered dead by apparent suicide by hanging in a building at the RIKEN facility in Kobe, Japan. On September 24, 2015, the RIKEN scientists reported that Obokata's STAP cells came from embryonic stem cell contamination, while on the same day, research groups who had attempted to reproduce the STAP protocol jointly reported that they had found it irreproducible.
260:
One previous way of creating stem cells has been via genetic manipulation of adult cells into iPS cells. Progress on iPS-based therapies has been slow due to regulatory hurdles surrounding genetic manipulation. Additionally, iPS techniques have an observed efficiency of around 1%, significantly lower
210:
papers were released, all scientists who tried to duplicate
Obokata's results failed and suspicion arose that her results were due to error or fraud. An investigation into alleged irregularities was launched by RIKEN on February 15, 2014. The allegations questioned the use of seemingly duplicated
253:, a pioneer of iPS research, called the findings "important to understand nuclear reprogramming ... a new approach to generate iPS-like cells". The idea that STAP cells can form placental tissue meant they could have made cloning considerably easier by bypassing the need for a donor egg and
244:
If the findings had proven to be valid, stimulus-triggered pluripotency cells could have been generated more easily and efficiently than by existing iPS techniques. Adapted to human tissue, the technique could have led to cheap and simple procedures to create patient-specific stem cells. Stem-cell
219:
On March 11, Teruhiko
Wakayama, one of Obokata's coauthors, urged all the researchers involved to withdraw the articles, citing many "questionable points". Charles Vacanti said he opposed their retraction and posted a "revised protocol" for creating STAP cells on his own website, which was taken
191:
Initially
Obokata's findings were met with skepticism, even among her coworkers. "Everyone said it was an artefact – there were some really hard days", she recalled. The manuscript describing the work was rejected multiple times before its eventual publication as an article (together with a
223:
On March 14, RIKEN released an interim report of the investigation. Out of the six items being investigated, the committee concluded that there was inappropriate handling of data on two items, but did not judge the mishandling as research misconduct. On April 1, RIKEN concluded that
Obokata had
215:
also announced that they were investigating. Several stem-cell scientists defended
Obokata or reserved their opinion while the investigation was ongoing. To address the problem of reproducibility in other laboratories, Obokata published some technical 'tips' on the protocols on March 5 while
1190:
Obokata, Haruko; Sasai, Yoshiki; Niwa, Hitoshi; Kadota, Mitsutaka; Andrabi, Munazah; Takata, Nozomu; Tokoro, Mikiko; Terashita, Yukari; Yonemura, Shigenobu; Vacanti, Charles A.; Wakayama, Teruhiko (January 29, 2014). "Bidirectional developmental potential in reprogrammed cells with acquired
1028:
De Los
Angeles, Alejandro; Ferrari, Francesco; Fujiwara, Yuko; Mathieu, Ronald; Lee, Soohyun; Lee, Semin; Tu, Ho-Chou; Ross, Samantha; Chou, Stephanie; Nguyen, Minh; Wu, Zhaoting; Theunissen, Thorold W.; Powell, Benjamin E.; Imsoonthornruksa, Sumeth; Chen, Jiekai; Borkent, Marti; Krupalnik,
227:
In the wake of the controversy, observers, journalists, and former members of RIKEN have stated that the organization is riddled with unprofessional and inadequate scientific rigor and consistency, and that this is reflective of serious issues with scientific research in Japan in general.
110:
mice " to be healthy, fertile, and normal" after one-to-two years of observation. Additionally, these mice produced healthy offspring, thereby demonstrating germline transmission which is "a strict criterion for pluripotency as well as genetic and epigenetic normality."
1029:
Vladislav; Lujan, Ernesto; Wernig, Marius; Hanna, Jacob H.; Hochedlinger, Konrad; Pei, Duanqing; Jaenisch, Rudolf; Deng, Hongkui; Orkin, Stuart H.; Park, Peter J.; Daley, George Q. (2015). "Failure to replicate the STAP cell phenomenon".
198:. A series of experiments, first turning a mouse embryo green by fluorescently tagging STAP cells, then videotaping the transformation of T-cells into pluripotent cells, finally convinced skeptics that the results were real.
136:
inhibitory mechanisms may block conversion to pluripotency. Research is underway to generate stimulus-triggered acquisition of pluripotency (STAP) cells using human tissue: in
February 2014, Charles Vacanti and Koji Kojima
35:
by subjecting ordinary cells to certain types of stress, such as the application of a bacterial toxin, submersion in a weak acid, or physical trauma. The technique gained prominence in
January 2014 when research by
231:
RIKEN commissioned a team of scientists to attempt to verify
Obokata's original results and asked Obokata to participate in the effort. On August 5, 2014, Obokata's supervisor and co-author of the original paper,
969:
Konno, Daijiro; Kasukawa, Takeya; Hashimoto, Kosuke; Itoh, Takehiko; Suetsugu, Taeko; Miura, Ikuo; Wakana, Shigeharu; Carninci, Piero; Matsuzaki, Fumio (2015). "STAP cells are derived from ES cells".
188:
from newborn mice could be transformed into cells that behaved much like stem cells. She repeated the experiment with other cell types including brain, skin, and muscle cells with the same result.
130:(iPS). It was not clear why ordinary cells do not convert into stem cells when subjected to similar stimuli under ordinary conditions, such as acidity in the body; Obokata et al. suggested that
522:
54:, was launched. On April 1, 2014, RIKEN concluded that Obokata had falsified data to obtain her results. On June 4, 2014, Obokata agreed to retract the papers. On August 5, 2014,
180:, she verified at the request of Charles Vacanti that some of the cultured cells she was working with shrank to the size of stem cells after being mechanically injured in a
950:
659:
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58:—Obokata's supervisor at RIKEN and one of the coauthors on the STAP cell papers—was found dead at a RIKEN facility after an apparent suicide by hanging.
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46:. Over the following months, all scientists who tried to duplicate her results failed, and suspicion arose that Obokata's results were due to error or
633:
434:
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141:
researchers originally involved in the discovery and publication of STAP) claimed to have preliminary results of STAP cells generated from human
1333:
184:. She went on as directed, to test the effects of various stimuli on cells. After modifying the technique, Obokata was able to show that
682:
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They put them in a weak acid solution (pH 5.7) for 30 minutes at 37°C, and then put them into petri dishes and grew them at normal pH.
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STAP would have been a radically simpler method of stem cell generation than previously researched methods as it requires neither
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771:
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of 5.7 for half an hour. Following this treatment, the cells were verified to be pluripotent by observing increasing levels of
470:
Obokata, Haruko; et al. (January 30, 2014). "Stimulus-triggered fate conversion of somatic cells into pluripotency".
409:
161:—could be spontaneously recovered from ordinary tissues that are stressed via mechanical injury or increased acidity.
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images in the papers, and reported failure to reproduce her results in other prominent stem-cell laboratories.
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called STAP cells "a major scientific discovery that will be opening a new era in stem-cell biology".
145:, but concomitantly cautioned that these preliminary results require further analysis and validation.
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543:"Breakthrough in stem cell creation using acid bath - What did the research involve?"
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168:(BWH), while she was studying as a post doc under Charles Vacanti, and then at the
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The technique for producing STAP cells was subsequently studied by
Obokata at the
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and Martin Vacanti conducted studies that led them to the idea that stem cells—
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Essential technical tips for STAP cell conversion culture from somatic cells
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660:"Exclusive: The miracle cure - scientists turn human skin into stem cells"
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608:"Simple way to make stem cells in half an hour hailed as major discovery"
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expressed in embryonic stem cells) over the following week using an Oct4-
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promising that the detailed procedure would be published in due course.
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816:"Interim report on the investigation of the Obokata et al. articles"
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spleen cells to certain stresses including an acidic medium with a
132:
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1289:
410:"Japan researcher agrees to withdraw disputed stem cell paper"
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Haruko Obokata, Yoshiki Sasai and Hitoshi Niwa (March 2014).
173:
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804:. Center for Tissue Engineering & Regenerative Medicine.
802:
PROTOCOL FOR GENERATING STAP CELLS FROM MATURE SOMATIC CELLS
625:
968:
1021:
910:‘STAPgate’ shows Japan must get back to basics in science
634:"Extraordinary stem cell method tested in human tissue"
569:"Stem cell power unleashed after 30 minute dip in acid"
88:
1189:
114:
STAP cells were supposedly able to differentiate into
699:. The Asahi Shimbun. January 30, 2014. Archived from
201:
192:
shorter jointly-written "letter") within the journal
18:
Proposed method of generating pluripotent stem cells
465:
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839:"Report on STAP Cell Research Paper Investigation"
697:"STAP cell pioneer nearly gave up on her research"
80:claimed that STAP cells were produced by exposing
962:
1310:
452:
379:Kameda, Masaaki; Otake, Tomoko (April 1, 2014).
716:"Acid-bath stem-cell study under investigation"
651:
381:"Obokata falsified data in STAP papers: probe"
22:Stimulus-triggered acquisition of pluripotency
836:
813:
435:"STAP paper co-author Sasai commits suicide"
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378:
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951:STAP paper co-author Sasai commits suicide
325:"Acid bath offers easy path to stem cells"
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862:"Research integrity: Cell-induced stress"
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1303:Stress turns ordinary cells pluripotent
1149:"Stem cells: Reprogramming with low pH"
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929:Ongoing Obokata story seeks out scandal
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714:Cyranoski, David (February 17, 2014).
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28:) was a proposed method of generating
1334:Discovery and invention controversies
1153:Nature Reviews Molecular Cell Biology
772:"Prof. wants STAP findings withdrawn"
680:
560:
352:"Stem cell 'major discovery' claimed"
350:Gallagher, James (January 29, 2014).
323:Cyranoski, David (January 29, 2014).
261:than the claimed efficiency of STAP.
220:down after he resigned his BWH post.
50:. An investigation by her employer,
683:"New Method for Reprogramming Cells"
586:
172:Center for Developmental Biology in
761:. Nature Protocols Discussion Forum
631:
567:Thomson, Helen (January 29, 2014).
13:
1305:News release at RIKEN with videos.
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658:Connor, Steve (February 9, 2014).
343:
202:Investigation into disputed claims
14:
1365:
1299:by Haruko Obokata, March 25, 2016
1283:
681:Grens, Kerry (January 29, 2014).
814:Press Release (March 14, 2014).
778:. March 11, 2014. Archived from
606:Sample, Ian (January 29, 2014).
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837:Press Release (April 1, 2014).
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1253:Update on the STAP cell papers
128:induced pluripotent stem cells
1:
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118:cells, meaning they would be
408:Elaine Lies (June 4, 2014).
206:In the months after the two
176:. In 2008, while working at
166:Brigham and Women's Hospital
7:
1260:"The rise and fall of STAP"
264:
72:
10:
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860:Cyranoski, David (2014).
730:10.1038/nature.2014.14738
331:. Nature Publishing Group
245:researcher Dusko Ilic of
800:Charles A Vacanti (2014)
65:nor the introduction of
40:et al. was published in
1295:March 31, 2016, at the
959:, August 6, 2014, p. 1
178:Harvard Medical School
1349:2014 in biotechnology
1329:Medical controversies
1226:(Retracted, see
1147:Baumann, Kim (2014).
937:, July 5, 2014, p. 19
505:(Retracted, see
281:Stem cell controversy
247:King's College London
67:transcription factors
703:on January 30, 2014.
541:(January 30, 2014).
153:In the early 2000s,
124:embryonic stem cells
97:transcription factor
1232:10.1038/nature13599
1205:10.1038/nature12969
1105:2015Natur.525..426.
1099:(7570): 426. 2015.
1051:10.1038/nature15513
1043:2015Natur.525E...6D
991:10.1038/nature15366
983:2015Natur.525E...4K
878:2014Natur.511..140C
776:The Yomiuri Shimbun
662:. independent.co.uk
511:10.1038/nature13598
484:10.1038/nature12968
1324:Induced stem cells
927:Schreiber, Mark, "
271:Induced stem cells
1339:Hoaxes in science
1272:"The Stress Test"
1199:(7485): 676–687.
782:on March 17, 2014
478:(7485): 641–647.
186:white blood cells
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1245:Retraction Watch
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1089:"STAP revisited"
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1297:Wayback Machine
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1255:. March 6, 2014
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1191:pluripotency".
1166:10.1038/nrm3754
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1141:Further reading
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1290:STAP HOPE PAGE
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843:. Retrieved
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780:the original
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743:February 20,
741:. Retrieved
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612:The Guardian
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240:Implications
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956:Japan Times
934:Japan Times
915:Japan Times
666:February 9,
617:January 31,
578:January 31,
549:February 6,
545:. nhs.co.uk
539:NHS Choices
361:January 31,
335:January 30,
329:Nature News
143:fibroblasts
120:more potent
30:pluripotent
1319:Stem cells
1313:Categories
1159:(3): 149.
947:Kyodo News
292:References
33:stem cells
1175:1471-0072
1123:0028-0836
1059:0028-0836
999:0028-0836
822:March 17,
786:March 17,
444:August 5,
276:Muse cell
116:placental
108:chimaeric
104:transgene
1293:Archived
1240:24990752
1221:54564044
1213:24476891
1183:24518367
1131:26399791
1067:26399835
1007:26399834
896:25008506
738:87071842
643:March 7,
519:24990753
492:24476887
390:April 2,
356:BBC News
265:See also
255:in vitro
73:Overview
1101:Bibcode
1075:4458211
1039:Bibcode
1015:4471867
979:Bibcode
874:Bibcode
845:June 2,
841:. RIKEN
818:. RIKEN
500:4463394
419:June 4,
414:Reuters
149:History
139:Harvard
133:in vivo
1264:Nature
1238:
1234:,
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1193:Nature
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517:
513:,
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472:Nature
213:Nature
208:Nature
195:Nature
85:murine
43:Nature
1344:Riken
1217:S2CID
1071:S2CID
1011:S2CID
734:S2CID
496:S2CID
174:Japan
170:RIKEN
122:than
93:Oct-4
52:RIKEN
48:fraud
1236:PMID
1209:PMID
1179:PMID
1171:ISSN
1127:PMID
1119:ISSN
1063:PMID
1055:ISSN
1003:PMID
995:ISSN
892:PMID
847:2014
824:2014
788:2014
745:2014
668:2014
645:2014
619:2014
580:2014
551:2014
515:PMID
488:PMID
446:2014
421:2014
392:2014
363:2014
337:2014
82:CD45
26:STAP
1228:doi
1201:doi
1197:505
1161:doi
1109:doi
1097:525
1047:doi
1035:525
987:doi
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