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Record W4414028793 · doi:10.1101/2025.09.04.674322

Human pluripotent stem cell-derived atrioventricular node-like pacemaker cells exhibit biological conduction bridge properties in vitro and in vivo

2025· preprint· en· W4414028793 on OpenAlexafffund
Michelle Lohbihler, Amos A. Lim, Stéphane Massé, Maggie Kwan, Omar Mourad, Olya Mastikhina, Brandon M. Murareanu, Malak Elbatarny, Renu Sarao, Beiping Qiang, Wahiba Dhahri, Matthew L. Chang, Aimin Xu, Amine Mazine, Shahryar Khattak, Sara S. Nunes, Kumaraswamy Nanthakumar, Michael A. Laflamme, Stephanie Protze

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicNeuroscience and Neural Engineering
Canadian institutionsUniversity of TorontoToronto General HospitalUniversity Health Network
FundersCanadian Institutes of Health ResearchCanada Research ChairsCanada Foundation for Innovation
KeywordsAtrioventricular nodeIn vivoInduced pluripotent stem cellIn vitroBridge (graph theory)Cell biologyStem cellElectrical conduction system of the heartChemistryBiologyAnatomyMedicineCardiologyElectrocardiographyEmbryonic stem cellBiotechnologyBiochemistryTachycardiaGene

Abstract

fetched live from OpenAlex

Summary The atrioventricular node (AVN) ensures synchronized heart contractions by establishing the electrical connection between the atria and ventricles. Dysfunction of the pacemaker cells of the AVN leads to atrioventricular block (AV block), a life-threatening condition managed with electronic pacemakers (EPMs). EPMs have drawbacks that could be overcome by a human pluripotent stem cell (hPSC)-derived biological conduction bridge (BioCB). Recent studies demonstrated the differentiation of AVN-like cells from hPSCs, but their conduction properties upon engraftment in vivo remain unexplored. Here we report the generation of AVN-like pacemaker cells (AVNLPCs) from hPSCs using WNT and BMP signaling modulation. These AVNLPCs transcriptionally resemble fetal AVN pacemaker cells, exhibit pacemaker action potentials, and display unique AVN-like conduction properties. Notably, when transplanted into the guinea pig heart, AVNLPCs replicate the functional properties of the AVN. Our study highlights the potential of an AVNLPC-based BioCB as novel cell therapy to improve treatment for AV block patients.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.008
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.038
GPT teacher head0.222
Teacher spread0.184 · 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 teacher head, not a consensus.

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

Citations0
Published2025
Admission routes2
Has abstractyes

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