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Record W2943497585 · doi:10.1016/j.stemcr.2019.04.005

Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias

2019· article· en· W2943497585 on OpenAlexafffund
Rocco Romagnuolo, Hassan Masoudpour, Andreu Porta‐Sánchez, Beiping Qiang, Jennifer Barry, Andrew Laskary, Xiuling Qi, Stéphane Massé, Karl Magtibay, Hiroyuki Kawajiri, Jun Wu, Tamilla Valdman Sadikov, Janet Rothberg, Krishna M. Panchalingam, Emily Titus, Ren‐Ke Li, Peter W. Zandstra, Graham A. Wright, Kumaraswamy Nanthakumar, Nilesh R. Ghugre, Gordon Keller, Michael A. Laflamme

Bibliographic record

VenueStem Cell Reports · 2019
Typearticle
Languageen
FieldMedicine
TopicCardiac electrophysiology and arrhythmias
Canadian institutionsUniversity Health NetworkUniversity of TorontoToronto General HospitalToronto Rehabilitation InstituteSunnybrook Health Science CentreHealth Sciences Centre
FundersDepartment of Family and Community Medicine, University of TorontoPeter Munk Cardiac Centre, University Health NetworkToronto General Hospital Research Institute, University Health NetworkCanada First Research Excellence FundOntario Institute for Regenerative MedicineCanada Foundation for InnovationSunnybrook Research InstituteUniversity Health Network
KeywordsBiologyEmbryonic stem cellStem cellInternal medicineMyocyteCardiologyCell biologyGeneticsGene

Abstract

fetched live from OpenAlex

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.226
Teacher spread0.217 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations318
Published2019
Admission routes2
Has abstractyes

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