ArticleAmerican journal of physiology. Heart and circulatory physiology2013
Mesenchymal stem cells improve cardiac conduction by upregulation of connexin 43 through paracrine signaling.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- Trial
- Exercise training reinforces the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for ventricular ectopy and myocardial infarction injury.Journal of physiology and biochemistry · 2026Article
- Wnt/β-catenin signaling regulates cardiac Cx43 in a metabolic substrate-dependent manner.Journal of molecular and cellular cardiology plus · 2025Article
- Inhibition of Gap Junction Formation Prior to Implantation of Bone Marrow-Derived Mesenchymal Cells Improves Function in the Ischemic Myocardium.International journal of molecular sciences · 2023Article
- The role of P21-activated kinase (Pak1) in sinus node function.Journal of molecular and cellular cardiology · 2023Article
- Upregulated miR-206 Aggravates Deep Vein Thrombosis by Regulating GJA1-Mediated Autophagy of Endothelial Progenitor Cells.Cardiovascular therapeutics · 2022Article
- Connexin43 is Dispensable for Early Stage Human Mesenchymal Stem Cell Adipogenic Differentiation But is Protective against Cell Senescence.Biomolecules · 2019Article
- Engineering microenvironments towards harnessing pro-angiogenic potential of mesenchymal stem cells.Materials science & engineering. C, Materials for biological applications · 2019Article
- Phenotypic Variation Between Stromal Cells Differentially Impacts Engineered Cardiac Tissue Function.Tissue engineering. Part A · 2019Article
- Gap Junctions and Wnt Signaling in the Mammary Gland: a Cross-Talk?Journal of mammary gland biology and neoplasia · 2019Review
- Overexpression of miR-27b-3p Targeting Wnt3a Regulates the Signaling Pathway of Wnt/Oxidative medicine and cellular longevity · 2019Article
- Simplet-dependent regulation of β-catenin signaling influences skeletal patterning downstream of Cx43.Development (Cambridge, England) · 2018Article
- Physiologic, Pathologic, and Therapeutic Paracrine Modulation of Cardiac Excitation-Contraction Coupling.Circulation research · 2018Review
- Inhibitory effect of oxidative damage on cardiomyocyte differentiation from Wharton's jelly-derived mesenchymal stem cells.Experimental and therapeutic medicine · 2017Article
- Low-after-high glucose down-regulated Cx43 in H9c2 cells by autophagy activation via cross-regulation by the PI3K/Akt/mTOR and MEK/ERKEndocrine · 2017Article
- Restoring heart function and electrical integrity: closing the circuit.NPJ Regenerative medicine · 2017Review
- Modeling Electrophysiological Coupling and Fusion between Human Mesenchymal Stem Cells and Cardiomyocytes.PLoS computational biology · 2016Article
- Mesenchymal stem cells in cardiac regeneration: a detailed progress report of the last 6 years (2010-2015).Stem cell research & therapy · 2016Review
- Stem cell-based therapies to promote angiogenesis in ischemic cardiovascular disease.American journal of physiology. Heart and circulatory physiology · 2016Review
- Mesenchymal Stem Cells in Cardiology.Methods in molecular biology (Clifton, N.J.) · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mesenchymal stem cells (MSCs) were shown to improve cell survival and alleviate cardiac arrhythmias when transplanted into cardiac tissue; however, little is known about the mechanism by which MSCs modify the electrophysiological properties of cardiac tissue. We aimed to distinguish the influence of cell-cell coupling between myocytes and MSCs from that of MSC-derived paracrine factors on the spontaneous activity and conduction velocity (θ) of multicellular cardiomyocyte preparations. HL-1 cells were plated on microelectrode arrays and their spontaneous activity and θ was determined from field potential recordings. In heterocellular cultures of MSCs and HL-1 cells the beating frequency was attenuated (t(0h): 2.26 ± 0.18 Hz; t(4h): 1.98 ± 0.26 Hz; P < 0.01) concomitant to the intercellular coupling between MSCs and cardiomyocytes. In HL-1 monolayers supplemented with MSC conditioned media (ConM) or tyrode (ConT) θ significantly increased in a time-dependent manner (ConT: t(0h): 2.4 cm/s ± 0.2; t(4h): 3.1 ± 0.4 cm/s), whereas the beating frequency remained constant. Connexin (Cx)43 mRNA and protein expression levels also increased after ConM or ConT treatment over the same time period. Enhanced low-density lipoprotein receptor-related protein 6 (LRP6) phosphorylation after ConT treatment implicates the Wnt signaling pathway. Suppression of Wnt secretion from MSCs (IWP-2; 5 μmol/l) reduced the efficacy of ConT to induce phospho-LRP6 and to increase θ. Inhibition of β-catenin (cardamonin; 10 μmol/l) or GSK3-α/β (LiCl; 5 mmol/l) also suppressed changes in θ, further supporting the hypothesis that MSC-mediated Cx43 upregulation occurs in part through secreted Wnt ligands and activation of the canonical Wnt signaling pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.