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

Lohbihler, M.; Lim, A. A.; Masse, S.; Kwan, M.; Mourad, O.; Mastikhina, O.; Murareanu, B. M.; Elbatarny, M.; Sarao, R.; Qiang, B.; Dhahri, W.; Chang, M. L.; Xu, A. L. Y.; Mazine, A.; Khattak, S.; Nunes, S. S.; Nanthakumar, K.; Laflamme, M. A.; Protze, S. I.

2025-09-04 developmental biology Community evaluation
10.1101/2025.09.04.674322 bioRxiv
Show abstract

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.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.