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Stimulus-triggered acquisition of pluripotency

Stimulus-triggered acquisition of pluripotency (STAP) is a discredited method of cellular reprogramming proposed in 2014, in which differentiated somatic cells from newborn mice were claimed to acquire pluripotency through brief exposure to external stresses, such as a mildly acidic bath or physical trauma, without the need for genetic manipulation or transcription factor overexpression.^[1] The process purportedly involved treating cells like those from the spleen or blood with low-pH conditions (pH 5.7 for 30 minutes) followed by culture, resulting in cells that expressed pluripotency markers such as Oct4 and Nanog, formed teratomas, and contributed to chimeric embryos.^[2] However, subsequent investigations revealed fundamental flaws, including data fabrication and irreproducibility, leading to the full retraction of the original reports.^[3] The STAP phenomenon was first described in two papers published in Nature on January 29, 2014, led by Haruko Obokata at the RIKEN Center for Developmental Biology in Japan, with co-authors including Yoshiki Sasai and Charles Vacanti.^[2] These studies suggested that the stress-induced reprogramming activated an innate cellular response, potentially mimicking evolutionary mechanisms for totipotency in early embryos, and could revolutionize regenerative medicine by providing an efficient, non-genetic route to pluripotent stem cells.^[4] Initial excitement was tempered by immediate scrutiny, as independent labs struggled to replicate the findings, prompting allegations of image duplication and selective data reporting within weeks of publication.^[5] An internal RIKEN investigation, concluded in April 2014, found Obokata guilty of research misconduct for fabricating Western blot images and duplicating gel lanes, while senior authors like Sasai were faulted for inadequate supervision; Sasai, a prominent neurobiologist, died by suicide amid the scandal in August 2014.^[6] The papers were formally retracted on July 2, 2014, after four co-authors, including Obokata, agreed to the withdrawal, though Obokata initially resisted.^[3] Further analyses, including genomic sequencing, indicated that purported STAP cell lines were contaminated with existing embryonic stem cells, exhibiting genetic markers inconsistent with true reprogramming, such as mixed sex chromosomes and pre-existing pluripotency signatures.^[7] Multiple replication efforts, including a 2015 international collaboration involving seven labs led by researchers at Harvard Medical School and Boston Children's Hospital, conclusively failed to produce STAP cells, with no evidence of aggregate formation, pluripotency gene upregulation, or chimera contribution under optimized conditions.^[8] A separate Japanese study published in Scientific Reports in 2016 similarly reported low-frequency Oct4 expression but no stable pluripotent lines or functional outcomes from stress-treated cells.^[9] These negative results, detailed in Nature companion papers, underscored the absence of a genuine STAP mechanism and attributed the original observations to contamination and experimental artifacts.^[10] The episode highlighted critical challenges in stem cell research, including the pressures of high-stakes publishing and the need for rigorous validation, but left no viable scientific legacy for STAP as a reprogramming technique.^[11]

Background Concepts

Pluripotent Stem Cells

Pluripotent stem cells are defined as undifferentiated cells capable of self-renewal and differentiation into all cell types of the three primary germ layers—ectoderm, mesoderm, and endoderm—thus forming any tissue in the body.^[12] This defining property distinguishes them from multipotent stem cells, which are limited to specific lineages, and totipotent cells, which can also contribute to extra-embryonic tissues.^[13] Key characteristics of pluripotent stem cells include the expression of core transcription factors such as Oct4, Sox2, and Nanog, which form a regulatory network essential for maintaining self-renewal and preventing differentiation.^[14] In vivo, their pluripotency is functionally validated through the formation of teratomas—tumors containing derivatives of all three germ layers—when injected into immunodeficient mice, and by their ability to contribute to chimeric organisms, integrating into host embryos to form viable, functional tissues across multiple lineages.^[15]^[16] Naturally occurring pluripotent stem cells are primarily embryonic stem cells (ESCs), derived from the inner cell mass of blastocyst-stage embryos.^[17] Induced pluripotent stem cells (iPSCs), generated by reprogramming somatic cells using transcription factors like Oct4, Sox2, Klf4, and c-Myc (the Yamanaka factors), represent an artificial source that circumvents ethical concerns associated with embryo destruction.^[18] Biologically, pluripotent stem cells play a central role in early embryonic development by giving rise to the foundational lineages that build the organism, while their unlimited self-renewal capacity positions them as a cornerstone for regenerative medicine, enabling the generation of patient-specific cells for tissue repair and disease modeling without relying on embryonic sources.^[19]^[20] The isolation of mouse ESCs was first achieved in 1981 by Martin Evans and Matthew Kaufman, marking a breakthrough in culturing these cells from preimplantation embryos.^[21] Human ESCs were subsequently derived in 1998 by James Thomson from surplus IVF blastocysts, expanding their potential applications while sparking ethical debates.^[17] Somatic cell reprogramming, as exemplified by iPSCs, artificially recapitulates this pluripotency in mature cells.^[18]

Somatic Cell Reprogramming Techniques

Somatic cell reprogramming refers to the process of reversing the differentiated state of mature somatic cells to restore their potential to develop into any cell type, thereby generating induced pluripotent stem cells (iPSCs) capable of self-renewal and differentiation into all three germ layers.^[22] This technique builds on earlier discoveries in nuclear reprogramming, such as those demonstrated by John Gurdon in the 1960s using frog eggs, but focuses on direct conversion without the need for oocytes.^[22] The landmark method for somatic cell reprogramming was established in 2006 by Shinya Yamanaka and colleagues, who introduced four transcription factors—Oct4, Sox2, Klf4, and c-Myc (collectively known as OSKM)—into mouse embryonic or adult fibroblasts via retroviral vectors to induce pluripotency.^[18] This approach achieved reprogramming efficiencies of approximately 0.01-0.1%, with the resulting iPSCs demonstrating characteristics similar to embryonic stem cells, including teratoma formation and germline transmission.^[18] However, the use of integrating viral vectors raised concerns about genomic insertions, and the inclusion of c-Myc, an oncogene, increased the risk of tumorigenesis in reprogrammed cells due to its role in promoting cell proliferation and potentially activating cancer-related pathways.^[23] In 2007, the same group extended this protocol to human dermal fibroblasts, generating the first human iPSCs with comparable OSKM factors, though efficiencies remained low at around 0.02%.^[24] To address limitations of viral integration and oncogenic risks, alternative non-integrating approaches have been developed, including chemical reprogramming with small molecules that modulate signaling pathways and epigenetic states to replace or enhance transcription factor activity.^[25] For instance, cocktails of inhibitors targeting histone deacetylases, DNA methyltransferases, and TGF-β signaling have improved reprogramming efficiency by up to 100-fold in some protocols while avoiding genetic modifications.^[26] In 2023, a fully chemical protocol without transcription factors was reported for generating human iPSCs, shortening the process to about 40 days.^[27] Other non-integrating methods utilize synthetic mRNA encoding the reprogramming factors, which transiently express the transgenes without genomic insertion, achieving efficiencies of 1-2% in human fibroblasts, or Sendai virus vectors, RNA-based systems that self-eliminate after delivery and yield transgene-free iPSCs at rates exceeding 0.1%.^[28] These strategies prioritize safer, scalable production of iPSCs for therapeutic applications. Despite these advances, somatic cell reprogramming faces significant challenges, primarily epigenetic barriers that maintain cellular identity, such as high levels of DNA methylation at pluripotency gene promoters and repressive histone modifications like H3K27me3.^[29] These obstacles often result in incomplete reprogramming, where cells exhibit partial pluripotency, aberrant gene expression, or residual epigenetic memory from their somatic origin, limiting their differentiation potential and raising safety concerns for clinical use.^[30] Overcoming these barriers typically requires coordinated activation of pluripotency networks and erasure of somatic marks, a process that remains inefficient and variable across cell types. The timeline of somatic cell reprogramming milestones includes the generation of the first mouse iPSCs in 2006 by Yamanaka's team, followed by human iPSCs in 2007, which revolutionized regenerative medicine by providing patient-specific pluripotent cells without ethical issues associated with embryonic sources.^[18]^[24] This work culminated in the 2012 Nobel Prize in Physiology or Medicine, awarded jointly to Yamanaka and Gurdon for discoveries showing that mature cells can be reprogrammed to pluripotency.^[22]

The Proposed STAP Method

Original Protocol Description

The original protocol for stimulus-triggered acquisition of pluripotency (STAP) utilized somatic cells derived from newborn mice as the starting material, primarily including fibroblasts from embryonic or neonatal tissues and CD45+ lymphocytes isolated from the spleen or peripheral blood. These cells were selected for their accessibility and representation of differentiated states, contrasting with the genetic factor-based approaches in induced pluripotent stem cell (iPSC) reprogramming. The core stressor in the protocol was a sublethal acidic treatment, where cells were suspended in acidified Hanks' balanced salt solution (HBSS) at pH 5.7 and incubated for 30 minutes at 37°C to induce cellular stress without causing widespread death. Following the acid bath, cells were washed and resuspended in a serum-free medium, such as DMEM/F-12 supplemented with 2% B27 and 10 ng/mL leukemia inhibitory factor (LIF), and cultured for 2 days at 37°C in 5% CO₂ to allow initial recovery and potential fate conversion. Subsequently, the cells were plated on gelatin-coated dishes and maintained in 2i medium—comprising Glasgow minimal essential medium with 15% KnockOut Serum Replacement, non-essential amino acids, sodium pyruvate, β-mercaptoethanol, LIF, the GSK3 inhibitor CHIR99021 (3 μM), and the MEK inhibitor PD0325901—to promote the formation of dome-shaped colonies indicative of pluripotency, typically observed after 7–10 days. Alternative stressors, such as heat shock at 42°C for 30 minutes or mechanical trituration through a fine pipette, were noted as viable but less efficient options compared to the acid treatment. Verification of pluripotency in the resulting STAP cells involved monitoring activation of an Oct4-GFP reporter transgene, which lit up in approximately 25% of surviving cells by day 7 post-stress, signaling reprogramming. Further assessments included the formation of embryoid bodies in suspension culture, teratoma generation upon injection into immunocompromised mice, and contribution to chimeric mice via blastocyst injection, all without any genetic manipulation or nuclear transfer, distinguishing STAP from iPSC methods.

Claimed Cellular Mechanisms

The claimed cellular mechanisms underlying stimulus-triggered acquisition of pluripotency (STAP) center on a stress response hypothesis, wherein external stimuli, such as sublethal acidic exposure, activate DNA damage response pathways involving ATM and ATR kinases, culminating in epigenetic erasure of somatic cell identity. These pathways are posited to initiate a cascade that demethylates DNA and remodels chromatin, enabling the reactivation of silenced pluripotency loci without exogenous genetic manipulation. Key events in this process include the protonation of histone tails under acidic conditions, which neutralizes their positive charge and promotes chromatin decondensation, thereby facilitating transcriptional access to developmental regulators. This decondensation is accompanied by the upregulation of core pluripotency genes, such as Oct4 and Nanog, occurring endogenously without transgene overexpression, as indicated by gene expression profiling in the original STAP cells. Additionally, the mechanism involves increased H3K9 acetylation, a mark associated with open chromatin states conducive to pluripotency. The proposed pathway posits that stress first induces a transient totipotent state, allowing contribution to both embryonic and extra-embryonic lineages, before stabilizing into pluripotency through auxiliary signals like non-coding RNAs or metabolic reprogramming from oxidative phosphorylation to glycolysis. Supporting observations include global DNA demethylation in STAP cells, mirroring the epigenetic resetting seen in zygotic genome activation post-fertilization. Unlike induced pluripotent stem cell (iPSC) generation, which relies on forced expression of transcription factors like Oct4, Sox2, Klf4, and c-Myc, STAP was claimed to emulate natural embryonic stress signals for a more physiological and rapid transition to pluripotency.

Discovery and Initial Claims

Research Origins

Haruko Obokata, a young Japanese biologist, led the development of the stimulus-triggered acquisition of pluripotency (STAP) concept as a researcher at the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan. She earned her PhD in 2011 from Waseda University, where her thesis focused on sporelike cells involved in tissue repair mechanisms (The degree was revoked by Waseda University in November 2015 following an investigation into irregularities in the thesis.).^[31] After beginning her doctoral studies at Waseda University, Obokata joined the laboratory of Charles Vacanti at Harvard Medical School's Brigham and Women's Hospital in 2009 as a research fellow, where she conducted experiments on tissue engineering and cellular stress responses while completing her PhD in 2011. Her work on STAP originated during this period at Harvard (2009–2011), where she explored how external stresses could alter cell fate, drawing inspiration from the natural regenerative abilities observed in amphibians like salamanders.^[32] These early experiments involved applying mechanical stress and chemical treatments to mammalian cells, leading to unexpected formations of cell colonies that exhibited markers of pluripotency. Upon returning to Japan in the fall of 2011 to take up a position at RIKEN CDB under the initial supervision of Teruhiko Wakayama and later the mentorship of Yoshiki Sasai, she shifted focus more intensively to mammalian systems, refining protocols to induce pluripotency without genetic modifications. This built on her prior observations and aimed to provide a simpler alternative to established somatic cell reprogramming techniques, such as those developed by Shinya Yamanaka. The research was supported by RIKEN's institutional resources and Japanese government grants allocated to the center for developmental biology studies.^[32]^[33] The motivations behind Obokata's STAP investigations centered on advancing regenerative medicine through a transgene-free method that mimicked evolutionary conserved stress-induced reprogramming seen in lower organisms, potentially enabling easier production of pluripotent cells for therapeutic applications. Funding came primarily from RIKEN, a national research institute receiving substantial support from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), which provided grants for exploratory stem cell and tissue engineering projects.^[32]^[34] Prior to public announcement, Obokata's team faced significant pre-publication challenges. In 2012, initial manuscripts were rejected by Nature, Science, and Cell due to concerns over insufficient evidence of true cellular reprogramming. With Sasai's guidance, revisions were made in 2013, incorporating additional data from acid treatments and collaborations with Teruhiko Wakayama's group on stem cell validation. Internal RIKEN reviews during this period raised questions about data presentation and reproducibility, but the project was approved for resubmission after addressing these issues through experimental refinements.^[32]^[35]^[36]

2014 Publications and Announcements

On January 29, 2014, two articles detailing the stimulus-triggered acquisition of pluripotency (STAP) method were published in Nature. The primary article, titled "Stimulus-triggered fate conversion of somatic cells into pluripotency," led by Haruko Obokata and co-authored by over 15 researchers including Yoshiki Sasai and Charles A. Vacanti, described the protocol for inducing pluripotency in mouse somatic cells through brief exposure to acidic conditions or mechanical stress, without genetic manipulation or nuclear transfer.^[37] The accompanying article, "Bidirectional developmental potential in reprogrammed cells with acquired pluripotency," further reported that STAP cells exhibited the ability to contribute to both embryonic and extra-embryonic tissues in chimeric mouse embryos.^[38] The publications claimed successful generation of STAP cells from a variety of mouse tissues, including those from the skin, lung, blood, and liver, with efficiencies reaching up to 25% under optimized conditions.^[37] Pluripotency was verified through teratoma formation, contribution to chimeric mice, and, in select cases, germline transmission, where STAP-derived cells produced viable offspring.^[38] These findings positioned STAP as a potentially simpler alternative to induced pluripotent stem cell reprogramming, with implications for regenerative medicine. The following day, on January 30, 2014, RIKEN, the Japanese research institute overseeing the work, held a press conference to announce the STAP discovery, describing it as a "fundamental breakthrough" that could transform therapeutic cell production by enabling rapid, non-genetic reprogramming of patient cells.^[39] The announcements generated widespread media excitement, with global outlets highlighting the simplicity of the "acid bath" technique; for instance, Nature News proclaimed "Acid bath offers easy path to stem cells," while Ars Technica reported "Acid bath turns cells from any tissue into stem cells."^[39]^[40] In Japan, Obokata, then 30 years old, was portrayed as a scientific prodigy, featuring prominently in television interviews and magazine covers as a rising star in stem cell research.^[41] Initial attempts at replication amplified the enthusiasm, with some international labs reporting partial successes in February 2014, such as transient expression of pluripotency markers like Oct4 in stressed cells, which encouraged further investment in the method before broader challenges arose.^[42]

Controversy and Scientific Scrutiny

Reproducibility Failures

Following the publication of the STAP papers in January 2014, numerous laboratories around the world initiated replication attempts in February and March, but none reported success in generating the claimed pluripotent cells. For instance, stem cell researcher Paul Knoepfler at the University of California, Davis, documented ongoing efforts in his laboratory and others during this period, noting by March 10 that no STAP cells had been produced despite following the published protocol. Similarly, independent attempts, such as those by Kenneth Ka Ho Lee at the Chinese University of Hong Kong, also failed to yield the expected results by early April. These early failures highlighted the protocol's apparent lack of robustness, with researchers reporting variability in cell survival and no consistent activation of pluripotency markers. Key challenges in replication centered on inconsistent colony formation and the inability of purported STAP cells to demonstrate true pluripotency. In controlled replication studies, cells exposed to the acid stress treatment occasionally formed autofluorescent spheres, but these did not exhibit stable pluripotency, as evidenced by their failure to contribute to tetraploid complementation assays—a stringent test requiring integration into chimeric embryos to form viable offspring. Further analyses, including genomic sequencing, later revealed that purported STAP cell lines were contaminated with existing embryonic stem cells, showing genetic inconsistencies such as mixed sex chromosomes.^[7] In 2015, multiple groups, including those at Harvard Medical School, conducted over 130 such attempts across various cell types and stress conditions, all resulting in non-pluripotent outcomes without genetic manipulation. These issues suggested that any observed effects were likely artifacts rather than a novel reprogramming mechanism. Data anomalies in the original publications further eroded confidence in the findings. Examination of the figures revealed splicing errors, such as duplicated lanes in gel electrophoresis images where separate experiments appeared combined without disclosure, as identified by the RIKEN investigating committee in April 2014. By that time, even Obokata's own laboratory at RIKEN had been unable to internally reproduce the STAP phenomenon under supervised conditions, prompting admissions of methodological inconsistencies. The scientific community responded swiftly through informal critiques on blogs, forums, and preprints, pointing to ambiguities in the protocol, such as undefined precise conditions for the acid bath (e.g., exact pH duration and buffering). Prominent stem cell experts, including Shoukhrat Mitalipov, highlighted these flaws in public discussions, arguing that the lack of detailed parameters made replication untenable. By late March 2014, co-author Charles Vacanti publicly requested an investigation into the papers, effectively distancing himself from the claims amid growing doubts.

Investigations and Retractions

Following the initial reports of reproducibility issues in early 2014, RIKEN, the Japanese research institute where lead author Haruko Obokata conducted much of the work, launched an official investigation into allegations of data manipulation and plagiarism in the STAP papers on February 20, 2014.^[43] The investigative committee's report, released on April 1, 2014, identified two instances of research misconduct by Obokata: the duplication and manipulation of lanes in electrophoresis gel images used to demonstrate Oct4 gene expression in STAP cells.^[44]^[45] Although the committee concluded these were acts of misconduct rather than intentional fabrication at the time, it recommended retraction of the papers due to the severity of the irregularities.^[6] Obokata appealed the findings, prompting a review committee that upheld the misconduct ruling on May 8, 2014, while emphasizing the need for further verification of the STAP phenomenon itself.^[46] Escalation continued with independent scrutiny from the publisher, Springer Nature (which owns Nature), which examined the raw data and images. Amid mounting pressure, co-author Yoshiki Sasai, RIKEN's deputy director and a prominent neuroscientist, died by suicide on August 5, 2014, leaving a note citing intense media scrutiny and institutional stress related to the controversy.^[47] On July 2, 2014—prior to the final appeal outcome—both Nature papers were retracted after Obokata and other authors failed to produce original raw data supporting key figures, such as DNA sequencing results and chimeric mouse images; the retraction notice cited irreproducible results and "critical errors" in data presentation, though Obokata maintained the science was valid and described the issues as honest mistakes.^[48]^[49] The institutional fallout intensified in late 2014. A RIKEN verification team, including external experts, attempted to replicate STAP cells but failed by December 17, 2014, leading Obokata to resign from her position at the RIKEN Center for Developmental Biology on December 19, 2014.^[50] Co-author Charles Vacanti, from Harvard Medical School and Brigham and Women's Hospital, who had initially defended the work, withdrew his support following the failed replications and evidence of data inconsistencies, stating in 2015 that he could no longer endorse the claims.^[51] RIKEN's final report in December 2014 confirmed fabrication in multiple figures and concluded that STAP cells likely did not exist as described. Legal proceedings ensued but resulted in no criminal charges. Japanese prosecutors investigated potential fraud in early 2015 after accusations that Obokata had misused research funds and materials, but declined to file charges, citing insufficient evidence of criminal intent.^[52] The episode underscored failures in peer review, as Nature later noted that the journal's process could not detect the extent of data misrepresentation without raw materials, prompting calls for enhanced pre-publication checks on images and data integrity.^[49]

Aftermath and Scientific Legacy

Impact on Stem Cell Research

The STAP controversy served as a temporary setback for research into stress-based cellular reprogramming, prompting many labs to pause or abandon efforts focused on external stimuli like acid treatment due to widespread reproducibility failures. Numerous independent attempts in the years following the 2014 publications confirmed that the claimed pluripotency induction could not be replicated, leading to heightened skepticism toward similar non-genetic approaches and a redirection of resources.^[11] This shift renewed emphasis on validating established induced pluripotent stem cell (iPSC) protocols, with researchers prioritizing robust controls and orthogonal assays to confirm pluripotency markers before advancing to functional tests like chimera formation.^[3] On a positive note, the scandal spurred greater investment in reproducibility across stem cell research, including funding for standardized protocols and validation tools. For instance, the International Society for Stem Cell Research (ISSCR) released global standards in 2023 to enhance rigor, mandating detailed reporting of cell line authentication, experimental conditions, and statistical analyses to mitigate future validation issues.^[53] Additionally, post-2014 adoption of CRISPR-based tools has enabled precise epigenetic tracking in pluripotency studies, allowing researchers to monitor DNA methylation and histone modifications during reprogramming with unprecedented resolution.^[54] As of 2025, isolated efforts to revisit STAP-like acid stress methods have consistently failed to yield pluripotent cells, underscoring the absence of any validated stimulus-triggered protocol. The field has instead pivoted toward partial reprogramming strategies for applications like anti-aging, where transient exposure to reprogramming factors rejuvenates cellular function without full dedifferentiation, as demonstrated by small-molecule cocktails that extend lifespan in aged human cells.^[55] Broader progress in chemical iPSC generation during the 2020s, relying on defined small-molecule combinations to induce pluripotency, has overshadowed the STAP episode, offering safer, integration-free alternatives for regenerative medicine.^[56] In response to the image manipulation issues central to the retractions, journals implemented stricter pre-publication screening, including automated software for detecting gel splicing and duplication in figures, while preprints faced amplified community scrutiny via platforms like PubPeer.^[3]

Lessons in Research Integrity

The STAP cells controversy underscored the critical importance of reproducibility in scientific research, as independent attempts to replicate the stimulus-triggered acquisition of pluripotency failed repeatedly, revealing that the reported results stemmed from contamination rather than a novel mechanism.^[11] Multiple laboratories, including those in Japan and the United States, confirmed the absence of STAP phenomena, emphasizing that extraordinary claims require robust, verifiable evidence beyond initial publications.^[8] This failure highlighted how premature announcements of breakthroughs can mislead the field, prompting calls for mandatory replication studies prior to widespread adoption.^[57] Peer review processes were exposed as insufficient safeguards against misconduct, as the original STAP papers passed scrutiny at a prestigious journal despite evident image manipulations and methodological inconsistencies.^[6] Investigators at RIKEN identified two instances of research misconduct by the lead author, including selective data presentation, yet these issues evaded initial detection, illustrating the limitations of anonymous review in high-stakes, paradigm-shifting work.^[58] The scandal prompted reflections on enhancing peer review through post-publication scrutiny and open data sharing to foster greater accountability.^[59] Intense academic pressures, particularly on early-career researchers, emerged as a root cause of the misconduct, with the drive for groundbreaking discoveries exacerbating tendencies toward data fabrication or selective reporting.^[60] In Japan's research environment, job insecurity and a culture intolerant of failure at institutions like RIKEN contributed to secrecy and inadequate oversight, allowing flawed work to progress unchecked.^[61] Surveys indicate that such pressures lead a notable minority of scientists—up to 2% admitting to falsification—to compromise integrity, underscoring the need for ethical training, supportive mentorship, and institutional policies that prioritize rigor over rapid publication.^[60] The aftermath reinforced the value of transparent investigations and swift retractions to preserve scientific integrity, as RIKEN's public inquiry and Nature's retraction of the papers helped mitigate long-term damage, though not without eroding public trust.^[48] This episode advocates for systemic reforms, including centralized databases for result verification and media guidelines to temper sensationalism, ensuring that future controversies strengthen rather than undermine the self-correcting nature of science.^[61] Ultimately, the STAP case serves as a cautionary tale, promoting a cultural shift toward valuing honest inquiry and collaborative validation over individual acclaim.^[59]

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[PDF] Report on STAP Cell Research Paper Investigation
Mar 31, 2014 · Obotaka was not familiar with the protocol, and that the description in the paper does not correspond exactly to the procedures followed in the ...
[42]
[PDF] Report on Review of Appeal of STAP Cell Research Paper ...
May 7, 2014 · On February 20, the appellant explained that she “superimposed the gel that presents a clean image of the band over the positive control of the ...
[43]
Stem-cell pioneer blamed media 'bashing' in suicide note - Nature
Aug 13, 2014 · Lawyer for Yoshiki Sasai's family reveals motive of Japanese researcher's act following STAP controversy.
[44]
STAP retracted - Nature
Jul 2, 2014 · This week, Nature publishes retractions of two high-profile papers that claimed a major advance in the field of stem cells (see page 112).Missing: Obokata | Show results with:Obokata
[45]
STAP stem cell papers officially retracted as Nature argues peer ...
Jul 2, 2014 · But only since the RIKEN investigation has it become clear that data that were an essential part of the authors' claims had been misrepresented.Missing: internal | Show results with:internal
[46]
Japanese scientist resigns as 'STAP' stem-cell method fails - Nature
Dec 19, 2014 · Haruko Obokata, the stem-cell biologist whose papers caused a sensation earlier this year before being retracted, has resigned from the RIKEN Center for ...
[47]
Managers of discredited STAP stem cell study refund salary - Science
Late on 23 October, RIKEN released a 5-point action plan [in Japanese here] to prevent a recurrence of research fraud. These included strengthening research ...Missing: investigation | Show results with:investigation
[48]
Public Response to Scientific Misconduct: Assessing Changes ... - NIH
Apr 20, 2017 · Riken finds Ms Obokata guilty of “two instances of research misconduct” in the STAP work [57]. Ms Obokata holds a press conference in order to ...Missing: internal | Show results with:internal
[49]
The ISSCR Releases Global Standards to Enhance Rigor and ...
Jun 5, 2023 · The ISSCR standards aim to enhance rigor in stem cell research, establish minimum criteria, and improve reproducibility, including a reporting ...
[50]
CRISPR Genome Engineering for Human Pluripotent Stem Cell ...
In this review, we discuss the opportunities and the challenges of repurposing bacterial nucleases for genome editing, while appreciating their roles.
[51]
Chemical reprogramming ameliorates cellular hallmarks of aging ...
Jun 30, 2025 · This study reveals that partial chemical reprogramming with defined small-molecule cocktails rejuvenates aged human cells and significantly extends lifespan ...
[52]
Induced pluripotent stem cells: Generation methods and a ... - Frontiers
In this study, we discuss the different methods of generation of iPSCs as well as their respective advantages and disadvantages.
[53]
Cell-induced stress - Ovid
The pro- cess, labelled stimulus-triggered acquisition of pluripotency (STAP), was so contrary to current thinking that some scientists said they accepted it ...
[54]
RIKEN finds two “instances of research misconduct” in STAP stem ...
Apr 1, 2014 · Japan's RIKEN research center has found misconduct in work that led to two controversial Nature papers, purporting to show an easy way to create stem cells.
[55]
Perspectives 10 years after STAP cells: the culture of science ...
Jan 29, 2024 · A stem cell biologist looks back on the scandal over STAP cells and now a decade later discusses whether science is doing better.
[56]
What pushes scientists to lie? The disturbing but familiar story of ...
Feb 18, 2015 · Above all, she maintained that her Stap (“stimulus-triggered acquisition of pluripotency”) cells really do exist. However, the existence of ...
[57]
STAP scandal a test of Japan's scientific integrity - Nikkei Asia
Jun 12, 2014 · In seeking to strike a balance between expediting research and managing risk, it is important to learn lessons from episodes such as the STAP ...