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Cells
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Advances in Cardiomyocyte and Stem Cell Biology in Heart Disease
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Advances in Cardiomyocyte and Stem Cell Biology in Heart Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Cardiovascular System".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 4052

Special Issue Editor

Dr. Ki Ho Park

E-Mail Website
Guest Editor
Division of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA
Interests: muscle physiology; ion channels; protein therapeutics; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Heart disease remains a leading cause of mortality and morbidity worldwide, necessitating the continuous exploration of innovative therapeutic approaches. Cardiomyocytes, as the fundamental contractile units of the heart, and stem cells, with their regenerative potential, have emerged as pivotal areas of study in understanding and addressing cardiac pathophysiology. This Special Issue will focus on the latest breakthroughs in cardiomyocyte biology and stem cell research, providing a platform to discuss advances in molecular mechanisms, regenerative strategies, and translational applications.

We welcome original research articles, reviews, and that highlight novel insights into cardiomyocyte function, the role of ion channels, protein therapeutics, and advancements in regenerative medicine. By bridging fundamental biology and clinical potential, this collection of papers will accelerate the development of effective treatments for heart disease. Contributions on innovative cell-based therapies, bioengineering approaches, and emerging biophysical tools are especially encouraged.

Dr. Ki Ho Park
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiomyocytes
  • stem cells
  • heart disease
  • regenerative medicine
  • ion channels
  • protein therapeutics
  • bioengineering
  • molecular biology

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Published Papers (4 papers)

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Research

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21 pages, 2532 KB  
Article
Electrophysiological Phenotyping of hiPSC-Derived Atrial Cardiomyocytes Using Automated Patch-Clamp: A Platform for Studying Atrial Inherited Arrhythmias
by Verónica Jiménez-Sábado, Hosna Babini, Peter C. Ruben, Eric A. Accili, Thomas W. Claydon, Leif Hove-Madsen and Glen F. Tibbits
Cells 2025, 14(24), 1941; https://doi.org/10.3390/cells14241941 - 6 Dec 2025
Viewed by 201
Abstract
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a robust platform for modelling inherited cardiac disorders. Comparative analysis of ion channel activity in patient-specific and isogenic control lines provides critical insights into the molecular mechanisms underlying channelopathies and arrhythmias. Atrial-specific hiPSC-CMs (hiPSC-aCMs) exhibit distinct [...] Read more.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a robust platform for modelling inherited cardiac disorders. Comparative analysis of ion channel activity in patient-specific and isogenic control lines provides critical insights into the molecular mechanisms underlying channelopathies and arrhythmias. Atrial-specific hiPSC-CMs (hiPSC-aCMs) exhibit distinct electrophysiological properties governed by unique ion channel expression profiles, underscoring the need for optimized methodologies to record atrial ionic currents accurately. Here, we characterized the electrophysiological features of hiPSC-aCMs using the Nanion Patchliner automated patch-clamp system. An optimized cell dissociation protocol was developed to enhance cell integrity and seal formation, while tailored intra- and extracellular solutions were employed to isolate specific ionic currents. Using this approach, we reliably recorded major atrial currents, including the sodium current (INa), L-type calcium current (ICaL), transient outward potassium current (Ito), ultrarapid component of the delayed rectifier current (IKur), small-conductance calcium-activated potassium current (ISK), and pacemaker funny current (If). The resulting current profiles were reproducible and consistent with those observed in native atrial cardiomyocytes. These findings establish the feasibility of the automated electrophysiological characterization of ion channels in hiPSC-aCMs. This platform enables more efficient investigation of pathogenic variants and facilitates the development of targeted therapeutics for atrial arrhythmias and related channelopathies. Full article
(This article belongs to the Special Issue Advances in Cardiomyocyte and Stem Cell Biology in Heart Disease)
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17 pages, 2028 KB  
Article
Dual Roles of Plasma miRNAs in Myocardial Injuries After Polytrauma: miR-122-5p and miR-885-5p Reflect Inflammatory Response, While miR-499a-5p and miR-194-5p Contribute to Cardiomyocyte Damage
by Jiaoyan Han, Liudmila Leppik, Larissa Sztulman, Roberta De Rosa, Victoria Pfeiffer, Lewin-Caspar Busse, Elena Kontaxi, Elisabeth Adam, Dirk Henrich, Ingo Marzi and Birte Weber
Cells 2025, 14(4), 300; https://doi.org/10.3390/cells14040300 - 18 Feb 2025
Viewed by 1241
Abstract
Cardiac injury after severe trauma is associated with higher mortality in polytrauma patients. Recent evidence suggests that miRNAs play a key role in cardiac pathophysiology and could serve as potential markers of cardiac damage after polytrauma. To explore this hypothesis, plasma miRNA profiles [...] Read more.
Cardiac injury after severe trauma is associated with higher mortality in polytrauma patients. Recent evidence suggests that miRNAs play a key role in cardiac pathophysiology and could serve as potential markers of cardiac damage after polytrauma. To explore this hypothesis, plasma miRNA profiles from polytrauma patients (ISS ≥ 16) with and without cardiac injury, stratified by troponin T levels (TnT, > 50 pg/mL vs. < 12 pg/mL), were analysed using NGS and validated via RT-qPCR. Five miRNAs (miR-122-5p, miR-424-5p, miR-885-5p, miR-194-5p, and miR-499a-5p) were found to be significantly upregulated in polytrauma patients with elevated TnT levels. miR-122-5p was associated with markers of right ventricular dysfunction (TAPSE) and left ventricular hypertrophy (IVS/LVPW), while miR-885-5p correlated with left ventricular hypertrophy (IVS/LVPW) and diastolic dysfunction (E/E’ ratio). In vitro, miR-194-5p mimic and miR-499a-5p mimic exhibited more active roles in cardiomyocyte injury by increasing caspase-3/7 activity and/or enhancing caspase-1 activity. Notably, the miR-194-5p mimic significantly enhanced the cytotoxic effects of the polytrauma cocktail, while miR-499a-5p boosted effects of LPS/nigericin stimulation in cardiomyocytes. Our findings identify miR-122-5p and miR-885-5p as potential biomarkers reflecting the cardiomyocyte response to polytrauma-induced inflammation, while miR-499a-5p and miR-194-5p appear to play a direct role in myocardial injury after polytrauma. Full article
(This article belongs to the Special Issue Advances in Cardiomyocyte and Stem Cell Biology in Heart Disease)
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Review

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20 pages, 1368 KB  
Review
Targeting Mitochondrial Dynamics via EV Delivery in Regenerative Cardiology: Mechanistic and Therapeutic Perspectives
by Dhienda C. Shahannaz, Tadahisa Sugiura, Brandon E. Ferrell and Taizo Yoshida
Cells 2025, 14(21), 1738; https://doi.org/10.3390/cells14211738 - 5 Nov 2025
Cited by 2 | Viewed by 954
Abstract
Mitochondrial dysfunction is a key contributor to cardiac injury and heart failure, and extracellular vesicles (EVs) have emerged as promising therapeutic agents due to their ability to deliver mitochondrial-targeted cargo. This review systematically maps the evidence on how EVs modulate mitochondrial dynamics—including fusion, [...] Read more.
Mitochondrial dysfunction is a key contributor to cardiac injury and heart failure, and extracellular vesicles (EVs) have emerged as promising therapeutic agents due to their ability to deliver mitochondrial-targeted cargo. This review systematically maps the evidence on how EVs modulate mitochondrial dynamics—including fusion, fission, mitophagy, and biogenesis—in regenerative cardiology. We comprehensively searched PubMed, Scopus, and Web of Science up to September 2025 for original studies. A total of 48 studies were included, with most utilizing EVs from mesenchymal stem cells, induced pluripotent stem cells, or cardiac progenitors. The review found that EV cargo influences key pathways such as DRP1 and MFN2, restores mitochondrial membrane potential, reduces ROS accumulation, and improves cardiomyocyte survival. While engineered EVs showed enhanced specificity, a lack of standardized preparation and quantitative assessment methods remains a significant challenge. We conclude that EV-mediated mitochondrial modulation is a promising strategy for cardiac repair, but the field needs harmonized protocols, deeper mechanistic understanding, and improved translational readiness to advance beyond preclinical research. The future of this research lies in integrating systems biology and precision targeting. Full article
(This article belongs to the Special Issue Advances in Cardiomyocyte and Stem Cell Biology in Heart Disease)
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28 pages, 680 KB  
Review
Cells Versus Cell-Derived Signals in Cardiac Regenerative Therapy: A Comparative Analysis of Mechanisms and Clinical Evidence
by Julia Soczyńska, Wiktor Gawełczyk, Krzysztof Majcherczyk, Julia Rydzek, Adrian Muzyka, Mateusz Żołyniak and Sławomir Woźniak
Cells 2025, 14(21), 1674; https://doi.org/10.3390/cells14211674 - 27 Oct 2025
Viewed by 1103
Abstract
Heart failure (HF) and other cardiac pathologies represent leading causes of hospitalization and mortality worldwide, underscoring the urgent need for effective regenerative therapies. In recent years, considerable research has focused on developing cell-based therapeutic strategies, with stem cells receiving particular attention. Approaches that [...] Read more.
Heart failure (HF) and other cardiac pathologies represent leading causes of hospitalization and mortality worldwide, underscoring the urgent need for effective regenerative therapies. In recent years, considerable research has focused on developing cell-based therapeutic strategies, with stem cells receiving particular attention. Approaches that harness cellular signaling pathways have also been investigated. Experimental studies conducted in both animal models and human subjects have demonstrated that cell-based therapies hold remarkable potential, showing efficacy through improvements in cardiac function, patient quality of life, and overall safety. Clinical data concerning therapies based on cellular signals, while sometimes inconclusive, often yield outcomes comparable to or even superior to those of cell-based interventions. Nonetheless, both approaches face substantial challenges, including the need to ensure reproducibility of results, standardization of therapeutic product preparation, and addressing ethical and regulatory considerations. To translate these promising strategies into clinical practice, a greater number of large-scale, multicenter, and diverse clinical trials will be required. Full article
(This article belongs to the Special Issue Advances in Cardiomyocyte and Stem Cell Biology in Heart Disease)
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