Search Results (7)

Cardiac tissue engineering is a promising strategy to restore cardiac function in heart failure patients. Understanding the cardiac tissue architecture including the cardiac stroma is essential for developing not only advanced cardiac tissue engineering but also novel therapeutic strategies. One of the crucial components of the cardiac stroma is the myocardial vasculature. To enhance the spatial visualization of the cardiac stromal cytoarchitecture with a particular focus on myocardial vasculature, we performed 3D reconstructions of the murine cardiac micro vessels using Serial Block-Face Scanning Electron Microscopy (SBF-SEM). These analyses revealed that pericyte cell bodies were primarily oriented lengthwise and extended several cellular protrusions towards the endothelium. At capillary branching points, some pericytes made contact with both capillaries emerging from branching. In addition to pericytes that are completely encapsulated by the common basal lamina together with capillary endothelial cells, we identified other vascular-associated cells located outside this sheath. Based on marker expression, these cells were distinguished from fibroblasts and suggested to be telocytes. The vascular-associated cells formed electron-dense contact zones with endothelial cells, suggesting functional coupling between these both cell types. In conclusion, this study provides detailed three-dimensional visualizations of the cardiac stroma with a particular focus on cardiac microvasculature, offering enhanced insight into the cardiac stromal cytoarchitecture. Full article

Unlike adult mammalian cardiomyocytes, cardiomyocytes in teleosts display high proliferative capacity throughout adulthood. This study aimed to identify the immunohistochemical profiles of cardiomyocytes and immune cells in the hearts of Molly fish by assessing the immunolabelling expression of key proteins involved in cell proliferation, differentiation, and tissue protection. The cardiac anatomy of Molly fish includes the atrium, ventricle, and bulbus arteriosus. The expression of SOX9, NF-κB, myostatin, and S100 proteins in myocardial cells indicates the proliferative features of the heart in Molly fish. The bulbus arteriosus is characterized by collagenous chambers and smooth muscle cells that express Ach and iba1. The atrium of Molly fish serves as a storage unit for rodlet cells and immune cells. Rodlet cells displayed immunoreactivity to NF-κB, iba1, Olig2, Ach, and S100 proteins, suggesting their roles in the immune response within the heart. Furthermore, telocytes (TCs) have emerged as a significant component of the atrium of Molly fish, expressing Ach, CD68, S100 protein, and iba1. These expressions indicate the involvement of TCs in multiple signaling pathways that contribute to heart architecture. This study delineates the intricate relationship between cardiomyocytes and innate immune cells in Molly fish. Full article

Because of cardiomyocyte death or dysfunction frequently caused by myocardial infarction (MI), heart failure is a leading cause of morbidity and mortality in modern society. Paradoxically, only limited and non-curative therapies for heart failure or MI are currently available. As a result, over the past two decades research has focused on developing cell-based approaches promoting the regeneration of infarcted tissue. Cell-based therapies for myocardial regeneration include powerful candidates, such as multipotent stem cells (mesenchymal stem cells (MSCs), bone-marrow-derived stem cells, endothelial progenitor cells, and hematopoietic stem cells) and induced pluripotent stem cells (iPSCs). These possess unique properties, such as potency to differentiate into desired cell types, proliferation capacity, and patient specificity. Preclinical and clinical studies have demonstrated modest improvement in the myocardial regeneration and reduced infarcted areas upon transplantation of pluripotent or multipotent stem cells. Another cell population that need to be considered as a potential source for cardiac regeneration are telocytes found in different organs, including the heart. Their therapeutic effect has been studied in various heart pathologies, such as MI, arrhythmias, or atrial amyloidosis. The most recent cell-free therapeutic tool relies on the cardioprotective effect of complex cargo carried by small membrane-bound vesicles—exosomes—released from stem cells via exocytosis. The MSC/iPSC-derived exosomes could be considered a novel exosome-based therapy for cardiovascular diseases thanks to their unique content. There are also other cell-free approaches, e.g., gene therapy, or acellular cardiac patches. Therefore, our review provides the most recent insights into the novel strategies for myocardial repair based on the regenerative potential of different cell types and cell-free approaches. Full article

Cardiac interstitium is a complex and dynamic environment, vital for normal cardiac structure and function. Telocytes are active cellular players in regulating main events that feature myocardial homeostasis and orchestrating its involvement in heart pathology. Despite the great amount of data suggesting (microscopically, proteomically, genetically, etc.) the implications of telocytes in the different physiological and reparatory/regenerative processes of the heart, understanding their involvement in realizing the heart’s mature cytoarchitecture is still at its dawn. Our scrutiny of the recent literature gave clearer insights into the implications of telocytes in the WNT signaling pathway, but also TGFB and PI3K/AKT pathways that, inter alia, conduct cardiomyocytes differentiation, maturation and final integration into heart adult architecture. These data also strengthen evidence for telocytes as promising candidates for cellular therapies in various heart pathologies. Full article

The regeneration of a diseased heart is one of the principal challenges of modern cardiovascular medicine. There has been ongoing research on stem-cell-based therapeutic approaches. A cell population called telocytes (TCs) described only 16 years ago largely contributed to the research area of cardiovascular regeneration. TCs are cells with small bodies and extremely long cytoplasmic projections called telopodes, described in all layers of the heart wall. Their functions include cell-to-cell signaling, stem-cell nursing, mechanical support, and immunoregulation, to name but a few. The functional derangement or quantitative loss of TCs has been implicated in the pathogenesis of myocardial infarction, heart failure, arrhythmias, and many other conditions. The exact pathomechanisms are still unknown, but the loss of regulative, integrative, and nursing functions of TCs may provide important clues. Therefore, a viable avenue in the future modern management of these conditions is TC-based cell therapy. TCs have been previously transplanted into a mouse model of myocardial infarction with promising results. Tandem transplantation with stem cells may provide additional benefit; however, many underresearched areas need to be addressed in future research before routine application of TC-based cell therapy in human subjects. These include the standardization of protocols for isolation, cultivation, and transplantation, quantitative optimization of TC transplants, cost-effectivity analysis, and many others. Full article

A great interest has developed over the last several years in research on interstitial Cajal-like cells (ICLCs), later renamed to telocytes (TCs). Such studies are restricted by diverse limitations. We aimed to critically review (sub)epicardial ICLCs/TCs and to bring forward supplemental immunohistochemical evidence on (sub)epicardial stromal niche inhabitants. We tested the epicardial expressions of CD117/c-kit, CD34, Cytokeratin 7 (CK7), Ki67, Platelet-Derived Growth Factor Receptor (PDGFR)-α and D2-40 in adult human cardiac samples. The mesothelial epicardial cells expressed D2-40, CK7, CD117/c-kit and PDGFR-α. Subepicardial D2-40-positive lymphatic vessels and isolated D2-40-positive and CK7-positive subepicardial cells were also found. Immediate submesothelial spindle-shaped cells expressed Ki-67. Submesothelial stromal cells and endothelial tubes were PDGFR-α-positive and CD34-positive. The expression of CD34 was pan-stromal, so a particular stromal cell type could not be distinguished. The stromal expression of CD117/c-kit was also noted. It seems that epicardial TCs could not be regarded as belonging to a unique cell type until (pre)lymphatic endothelial cells are inadequately excluded. Markers such as CD117/c-kit or CD34 seem to be improper for identifying TCs as a distinctive cell type. Care should be taken when using the immunohistochemical method and histological interpretations, as they may not produce accurate results. Full article

In this review, we describe the current knowledge on calcium signaling pathways in interstitial cells with a special focus on interstitial cells of Cajal (ICCs), interstitial Cajal-like cells (ICLCs), and telocytes. In detail, we present the generation of Ca²⁺ oscillations, the inositol triphosphate (IP₃)/Ca²⁺ signaling pathway and modulation exerted by cytokines and vasoactive agents on calcium signaling in interstitial cells. We discuss the physiology and alterations of calcium signaling in interstitial cells, and in particular in telocytes. We describe the physiological contribution of calcium signaling in interstitial cells to the pacemaking activity (e.g., intestinal, urinary, uterine or vascular pacemaking activity) and to the reproductive function. We also present the pathological contribution of calcium signaling in interstitial cells to the aortic valve calcification or intestinal inflammation. Moreover, we summarize the current knowledge of the role played by calcium signaling in telocytes in the uterine, cardiac and urinary physiology, and also in various pathologies, including immune response, uterine and cardiac pathologies. Full article