Myocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be viable and conjugated with the electromechanical syncytium of the recipient tissue, which is unattainable without an external scaffold substrate. On the other hand, the outer scaffold may hinder cell delivery, for example, making intramyocardial injection difficult. To resolve this contradiction, we developed molecular vehicles that combine a wrapped (rather than outer) polymer scaffold that is enveloped by the cell and provides excitability restoration (lost when cells were harvested) before engraftment. It also provides a coating with human fibronectin, which initiates the process of graft adhesion into the recipient tissue and can carry fluorescent markers for the external control of the non-invasive cell position. In this work, we used a type of scaffold that allowed us to use the advantages of a scaffold-free cell suspension for cell delivery. Fragmented nanofibers (0.85 µm ± 0.18 µm in diameter) with fluorescent labels were used, with solitary cells seeded on them. Cell implantation experiments were performed in vivo. The proposed molecular vehicles made it possible to establish rapid (30 min) electromechanical contact between excitable grafts and the recipient heart. Excitable grafts were visualized with optical mapping on a rat heart with Langendorff perfusion at a 0.72 ± 0.32 Hz heart rate. Thus, the pre-restored grafts’ excitability (with the help of a wrapped polymer scaffold) allowed rapid electromechanical coupling with the recipient tissue. This information could provide a basis for the reduction of engraftment arrhythmias in the first days after cell therapy.

Induced pluripotent stem cells (iPSCs) constitute a potential source of patient-specific human cardiomyocytes for a cardiac cell replacement therapy via intramyocardial injections, providing a major benefit over other cell sources in terms of immune rejection. However, intramyocardial injection of the cardiomyocytes has substantial challenges related to cell survival and electrophysiological coupling with recipient tissue. Current methods of manipulating cell suspensions do not allow one to control the processes of adhesion of injected cells to the tissue and electrophysiological coupling with surrounding cells. In this article, we documented the possibility of influencing these processes using polymer kernels: biocompatible fiber fragments of subcellular size that can be adsorbed to a cell, thereby creating the minimum necessary adhesion foci to shape the cell and provide support for the organization of the cytoskeleton and the contractile apparatus prior to adhesion to the recipient tissue. Using optical excitation markers, the restoration of the excitability of cardiomyocytes in suspension upon adsorption of polymer kernels was shown. It increased the likelihood of the formation of a stable electrophysiological coupling in vitro. The obtained results may be considered as a proof of concept that the stochastic engraftment process of injected suspension cells can be controlled by smart biomaterials.

The occurrence of atrial fibrillation (AF), one of the most socially significant arrhythmias, is associated with the presence of areas of fibrosis. Fibrosis introduces conduction heterogeneity into the cardiac tissue and, thus, may be a substrate for spiral wave reentry, which provokes the onset of AF and is often associated with its persistence. Despite results from computer and animal models of cardiac tissues, data on the conditions under which microreentries occur in human tissues are limited. In this work, we conducted a study of the new approach to modeling the fibrous atrial tissue, which takes into account the cellular structure and conduction in fibrosis areas. Using the Potts model, we created a realistic texture of atrial tissues remodeled by fibroblasts and showed the presence of pathways in such a system with a low proportion of fibroblasts. Our study revealed the relationship between the shape of the cells’ action potential, their location in the tissue, and the direction of the wave propagation. The wavefront obtained in the model creates a dynamic heterogeneity of the tissue, which affects the migration and pinning of spiral waves, and explains the formation of microreentries in the cardiac tissue. In the future, such a model can become a potential tool for predictive modeling of AF and the search for ablation target identification.

Cardiac arrhythmias are a major cause of cardiovascular mortality worldwide. Functional heterogeneity of cardiac tissue is an inevitable arrhythmogenic condition that may create nonlinear wave turbulence or reentry with subsequent arrhythmia initiation. The relation between propagation heterogeneity and the onset of reentry is of great theoretical and practical importance. Here, we present a conceptual representation of heterogeneous tissue expressed through alternating local and global tissue anisotropy with discreteness of membrane conductance. To contrast the influence of distributed heterogeneity, we investigated the interaction of a highfrequency wavetrain at a sharp anisotropy-symmetric obstacle. The revealed tendency of a heterogeneous system to form reentry was formalized into the single concept of a vulnerable frequency corridor that can be estimated experimentally. Using the joint in vitro–in silico approach, we defined an anomalous stable growth of a unidirectional block in the vicinity of an obstacle, depending on the direction of the anisotropy vector. This effect explains the limited applicability of homogeneous models to predicting the occurrence of primary reentry. Furthermore, computer simulations showed the special role played by other possible mechanisms of excitation, as ephaptic intercellular coupling, in the formation of a unidirectional

Background/Objectives: Patient-derived mesenchymal stem cells (MSCs) represent a promising avenue for myocardial regeneration, yet therapeutic application remains limited by inconsistent differentiation capacity and the absence of standardized cardiogenic induction protocols. This study demonstrates a proof-of-concept for guiding patient-specific bone marrow MSCs toward a functional cardiomyocyte phenotype using paracrine signals from differentiating iPSC-derived cardiomyocytes (iPSC-CMs). Materials and Methods: MSCs were maintained in conditioned medium from a concurrent, validated iPSC-CM differentiation protocol, with evaluation via immunocytochemistry, optical mapping, and whole-cell patch-clamp recordings. Results: Differentiated MSCs acquired organized sarcomeric architecture with cross-striations and displayed spontaneous calcium oscillations with decay kinetics matching source iPSC-CMs (CaT50 ≈ 283 ms vs. 301 ms). In co-culture, MSC-derived cells exhibited synchronized calcium dynamics with iPSC-CMs, confirming functional coupling, while patch-clamp detected hallmark cardiac ion currents (INa, ICa,L, and IKv). Morphologically, MSC-CMs displayed more mature, elongated rod-like shapes. Conclusions: Although current densities indicate partial immaturity, their reproducible detection validates successful cardiomyogenic commitment. This “parallel differentiation” platform eliminates donor-specific protocol tuning, providing a streamlined, paracrine-mediated approach to generate autologous cardiomyocyte-like cells for disease modeling, pharmacological testing, and future regenerative applications.

In the last decade,invitroexperiments have shown that mechanical properties of the bases could markedly influence the efficacy of differentiation of the induced pluripotent and embryonic stem cells and their development into the mature phenotype. By changing of mechanical, elastic and structural characteristics of the base, it is possible to increase the percentage of stem cells that differentiate to cardiomyocytes. The study was aimed at evaluation of the effects induced by changing physical characteristics of the base on the formation of phenotypic characteristics of cardiac cells. This included the comparison of structural properties of the cultured layer of heart tissue obtained by changing of elasticity and structure of polymeric bases. The results showed significant differences in calcium activity and structural characteristics of cardiomyocytes depending on the base properties, as well as significant variation in the excitation conduction. As long as conduction abnormalities in the heart tissues can often lead to occurrence of life-threatening cardiac arrhythmias, the results can be used to determine patient groups at increased risk of death from heart failure.