Modeling the atrioventricular conduction axis using human pluripotent stem cell-derived cardiac assembloids.

Autor:	Li J; Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Wiesinger A; Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Fokkert L; Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Bakker P; Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., de Vries DK; Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Tijsen AJ; Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Pinto YM; Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Verkerk AO; Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Christoffels VM; Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Boink GJJ; Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands., Devalla HD; Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands. Electronic address: h.d.devalla@amsterdamumc.nl.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Nov 07; Vol. 31 (11), pp. 1667-1684.e6. Date of Electronic Publication: 2024 Sep 10.
DOI:	10.1016/j.stem.2024.08.008
Abstrakt:	The atrioventricular (AV) conduction axis provides electrical continuity between the atrial and ventricular chambers. The "nodal" cardiomyocytes populating this region (AV canal in the embryo, AV node from fetal stages onward) propagate impulses slowly, ensuring sequential contraction of the chambers. Dysfunction of AV nodal tissue causes severe disturbances in rhythm and contraction, and human models that capture its salient features are limited. Here, we report an approach for the reproducible generation of AV canal cardiomyocytes (AVCMs) with in vivo-like gene expression and electrophysiological profiles. We created the so-called "assembloids" composed of atrial, AVCM, and ventricular spheroids, which effectively recapitulated unidirectional conduction and the "fast-slow-fast" activation pattern typical for the vertebrate heart. We utilized these systems to reveal intracellular calcium mishandling as the basis of LMNA-associated AV conduction block. In sum, our study introduces novel cell differentiation and tissue construction strategies to facilitate the study of complex disorders affecting heart rhythm. Competing Interests: Declaration of interests A patent related to the approaches described in this study has been filed with H.D.D. as inventor. Y.M.P. is a co-founder of ACS Biomarker BV, co-founder and Chief Medical Officer of Phlox Therapeutics BV, and Medical Director of Armgo Pharma. G.J.J.B. is a co-founder and Chief Executive Officer of PacingCure B.V. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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