Publications
302 results found
Fuchs M, Kreutzer FP, Kapsner LA, et al., 2020, Integrative Bioinformatic Analyses of Global Transcriptome Data Decipher Novel Molecular Insights into Cardiac Anti-Fibrotic Therapies, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 21
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- Citations: 12
Pitoulis F, Watson S, Perbellini F, et al., 2020, Myocardial slices come to age: An intermediate complexity in vitro cardiac model for translational research, Cardiovascular Research, Vol: 116, Pages: 1275-1287, ISSN: 0008-6363
Although past decades have witnessed significant reductions in mortality of heart failure together with advances in our understanding of its cellular, mo-lecular, and whole-heart features, a lot of basic cardiac research still fails to translate into clinical practice.In this review we examine myocardial slices, a novel modelin the translational arena. Myocardial slices are living ultra-thin sections of heart tissue. Slices maintain the myocardium’s native function (contractility, electrophysiology) and structure (multicellularity, extracellular matrix), and can be prepared from animal and human tissue. Thediscussion9beginswith the history and current advances in the model, the different in-terlaboratory methods of preparation and their potentialimpact on results. We then contextualise slices’ advantages and limitations by comparing itwith other cardiac models. Recently, sophisticated methods have enabled slices to be cultured chronically in vitro whilepreserving thefunctional and structural phenotype. This is more timely now than ever where chronic physiologically relevant in vitro platforms for assessment of therapeutic strategies are urgently needed. We interrogate the technological developments that have per-mitted this, their limitations, and future directions. Finally, we look into the general obstacles faced by the translational field, and how implementation of research systems utilising slices could help in resolving these.
Pitoulis FG, Hasan W, Papadaki M, et al., 2020, Intact myocardial preparations reveal intrinsic transmural heterogeneity in cardiac mechanics, Journal of Molecular and Cellular Cardiology, Vol: 141, Pages: 11-16, ISSN: 0022-2828
Determining transmural mechanical properties in the heart provides a foundation to understand physiological and pathophysiological cardiac mechanics. Although work on mechanical characterisation has begun in isolated cells and permeabilised samples, the mechanical profile of living individual cardiac layers has not been examined. Myocardial slices are 300 μm-thin sections of heart tissue with preserved cellular stoichiometry, extracellular matrix, and structural architecture. This allows for cardiac mechanics assays in the context of an intact in vitro organotypic preparation. In slices obtained from the subendocardium, midmyocardium and subepicardium of rats, a distinct pattern in transmural contractility is found that is different from that observed in other models. Slices from the epicardium and midmyocardium had a higher active tension and passive tension than the endocardium upon stretch. Differences in total myocyte area coverage, and aspect ratio between layers underlined the functional readouts, while no differences were found in total sarcomeric protein and phosphoprotein between layers. Such intrinsic heterogeneity may orchestrate the normal pumping of the heart in the presence of transmural strain and sarcomere length gradients in the in vivo heart.
King O, Cruz-Moreira D, Kermani F, et al., 2020, NON-MYOCYTE INFLUENCE ON EXCITATION-CONTRACTION COUPLING IN INDUCED PLURIPOTENT STEM CELL DERIVED MYOCARDIUM, Publisher: SPRINGER, Pages: 272-272, ISSN: 0920-3206
Bardi I, Dries E, Nunez-Toldra R, et al., 2020, The use of living myocardial slices as a novel disease model to study cardiac arrhythmogenicity in vitro, 23rd World Congress of the International-Society-for-Heart-Research (ISHR), Publisher: ELSEVIER SCI LTD, Pages: 49-50, ISSN: 0022-2828
Pitoulis FG, Terracciano CM, 2020, Heart Plasticity in Response to Pressure- and Volume-Overload: A Review of Findings in Compensated and Decompensated Phenotypes, FRONTIERS IN PHYSIOLOGY, Vol: 11, ISSN: 1664-042X
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- Citations: 29
Zwi Dantsis L, Wang B, Marijon C, et al., 2020, Remote magnetic nanoparticle manipulation enables the dynamic patterning of cardiac tissues, Advanced Materials, Vol: 32, Pages: 1-6, ISSN: 0935-9648
The ability to manipulate cellular organization within soft materials has important potential in biomedicine and regenerative medicine; however, it often requires complex fabrication procedures. Here, we develop a simple, cost-effective, and one-step approach that enables the control of cell orientation within 3-dimensional (3D) collagen hydrogels to dynamically create various tailored microstructures of cardiac tissues. This isachieved by incorporating iron-oxide nanoparticles into human cardiomyocytes (CMs) and applying a short-term external magnetic field to orient the cells along the applied field to impart different shapes without any mechanical supports. The patterned constructs areviable and functional, canbe detected by T2*-weighted MRI and induceno alteration to normal cardiac function after grafting onto rat hearts. This strategy paves the way to creating customized, macroscale, 3D tissue constructs with various cell-types for therapeutic and bioengineering applications, as well as providing powerful models for investigating tissue behavior.
Dries E, Bardi I, Pitoulis F, et al., 2020, A Novel <i>in vitro</i> Model using Organotypic Cardiac Slices Reveals Transmural Heterogeneity in Arrhythmogenic Ca<SUP>2+</SUP> Events after Cardiac Injury, 64th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 254A-254A, ISSN: 0006-3495
King O, Cruz-Moreira D, Kit-Anan SW, et al., 2020, Vascularized Myocardium-On-A-Chip: Excitation-Contraction Coupling in Perfused Cardiac Co-Cultures, 64th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 410A-410A, ISSN: 0006-3495
Pitoulis FG, Nunez-Toldra R, Kit-Anan WS, et al., 2020, Exploring Mechanical Load-Induced Cardiac Remodelling Using a Novel Organotypic Myocardial Slice Model, 64th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 425A-425A, ISSN: 0006-3495
Narodden S, 2019, Molecular and Cellular Basis of Cardiomyopathies, Heart of the Matter Key concepts in cardiovascular science, Editors: Terracciano, Guymer, Publisher: Springer Nature, ISBN: 9783030242190
Bridging the gap between clinics and basic biology, the book offers a valuable guide for medical students, and for Master and PhD students in Cardiovascular Biomedicine.
Fourre JD, Bardi I, King O, et al., 2019, Endothelial cell activation by pro-inflammatory cytokines exerts novel paracrine effects on cocultured cardiomyocytes, Publisher: WILEY, Pages: 91-91, ISSN: 1748-1708
Pitoulis F, Perbellini F, Harding SE, et al., 2019, Mechanical heterogeneity across the left ventricular wall - a study using intact multicellular preparations, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 3264-3264, ISSN: 0195-668X
Fourre J, Bardi I, Maughan RT, et al., 2019, Endothelial cell activation by pro-inflammatory cytokines exerts novel paracrine effects on co-cultured cardiomyocytes, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 3904-3904, ISSN: 0195-668X
Jabbour R, Owen T, Reinsch M, et al., 2019, Development and preclinical testing of upscaled engineered heart tissue for use in translational studies, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 3273-3273, ISSN: 0195-668X
Sanzari I, Dinelli F, Humphrey E, et al., 2019, Microstructured hybrid scaffolds for aligning neonatal rat ventricular myocytes, MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, Vol: 103, ISSN: 0928-4931
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- Citations: 1
Ou Q, Jacobson Z, Abouleisa R, et al., 2019, Physiological Biomimetic Culture System for Pig and Human Heart Slices, Circulation Research, Vol: 125, Pages: 628-642, ISSN: 0009-7330
RATIONALE: Preclinical testing of cardiotoxicity and efficacy of novel heart failure therapies faces a major limitation: the lack of an in situ culture system that emulates the complexity of human heart tissue and maintains viability and functionality for a prolonged time. OBJECTIVE: To develop a reliable, easily reproducible, medium-throughput method to culture pig and human heart slices under physiological conditions for a prolonged period of time. METHODS AND RESULTS: Here, we describe a novel, medium-throughput biomimetic culture system that maintains viability and functionality of human and pig heart slices (300 µm thickness) for 6 days in culture. We optimized the medium and culture conditions with continuous electrical stimulation at 1.2 Hz and oxygenation of the medium. Functional viability of these slices over 6 days was confirmed by assessing their calcium homeostasis, twitch force generation, and response to β-adrenergic stimulation. Temporal transcriptome analysis using RNAseq at day 2, 6, and 10 in culture confirmed overall maintenance of normal gene expression for up to 6 days, while over 500 transcripts were differentially regulated after 10 days. Electron microscopy demonstrated intact mitochondria and Z-disc ultra-structures after 6 days in culture under our optimized conditions. This biomimetic culture system was successful in keeping human heart slices completely viable and functionally and structurally intact for 6 days in culture. We also used this system to demonstrate the effects of a novel gene therapy approach in human heart slices. Furthermore, this culture system enabled the assessment of contraction and relaxation kinetics on isolated single myofibrils from heart slices after culture. CONCLUSIONS: We have developed and optimized a reliable medium-throughput culture system for pig and human heart slices as a platform for testing the efficacy of novel heart failure therapeutics and reliable testing of cardiotoxicity in a 3D heart
Wang BX, Kit-Anan W, Whittaker T, et al., 2019, Regulation of cardiac excitation-contraction coupling by human cardiac fibroblasts in health and disease, British-Pharmacology-Society Meeting (Pharmacology), Publisher: WILEY, Pages: 3034-3035, ISSN: 0007-1188
Watson S, Duff J, Bardi I, et al., 2019, Biomimetic electromechanical stimulation to maintain adult myocardial slices in vitro, Nature Communications, Vol: 10, ISSN: 2041-1723
Adult cardiac tissue undergoes a rapid process of dedifferentiation when cultured outside the body. The in vivo environment, particularly constant electromechanical stimulation, is fundamental to the regulation of cardiac structure and function. We investigated the role of electromechanical stimulation in preventing culture-induced dedifferentiation of adult cardiac tissue using rat, rabbit and human heart failure myocardial slices. Here we report that the application of a preload equivalent to sarcomere length (SL) = 2.2 μm is optimal for the maintenance of rat myocardial slice structural, functional and transcriptional properties at 24 h. Gene sets associated with the preservation of structure and function are activated, while gene sets involved in dedifferentiation are suppressed. The maximum contractility of human heart failure myocardial slices at 24 h is also optimally maintained at SL = 2.2 μm. Rabbit myocardial slices cultured at SL = 2.2 μm remain stable for 5 days. This approach substantially prolongs the culture of adult cardiac tissue in vitro.
Kreutzer FP, Meinecke A, Fiedler J, et al., 2019, HFWM: Natural compound-derived small molecules to target fibrosis, Publisher: WILEY, Pages: 319-319, ISSN: 1388-9842
Jabbour R, Owen T, Reinsch M, et al., 2019, DEVELOPMENT AND PRECLINICAL TESTING OF A LARGE HEART MUSCLE PATCH, Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ PUBLISHING GROUP, Pages: A157-A158, ISSN: 1355-6037
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- Citations: 3
Watson SA, Terracciano CM, Perbellini F, 2019, Myocardial sices: an intermediate complexity platform for translational cardiovascular research, Cardiovascular Drugs and Therapy, Vol: 33, Pages: 239-244, ISSN: 0920-3206
Myocardial slices, also known as "cardiac tissue slices" or "organotypic heart slices," are ultrathin (100-400 μm) slices of living adult ventricular myocardium prepared using a high-precision vibratome. They are a model of intermediate complexity as they retain the native multicellularity, architecture, and physiology of the heart, while their thinness ensures adequate oxygen and metabolic substrate diffusion in vitro. Myocardial slices can be produced from a variety of animal models and human biopsies, thus providing a representative human in vitro platform for translational cardiovascular research. In this review, we compare myocardial slices to other in vitro models and highlight some of the unique advantages provided by this platform. Additionally, we discuss the work performed in our laboratory to optimize myocardial slice preparation methodology, which resulted in highly viable myocardial slices from both large and small mammalian hearts with only 2-3% cardiomyocyte damage and preserved structure and function. Applications of myocardial slices span both basic and translational cardiovascular science. Our laboratory has utilized myocardial slices for the investigation of cardiac multicellularity, visualizing 3D collagen distribution and micro/macrovascular networks using tissue clearing protocols and investigating the effects of novel conductive biomaterials on cardiac physiology. Myocardial slices have been widely used for pharmacological testing. Finally, the current challenges and future directions for the technology are discussed.
Wang BX, Kit-Anan W, Whittaker T, et al., 2019, Human Cardiac Fibroblast-Secreted Exosomes Improve Efficiency of Human Cardiomyocyte Calcium Cycling, Publisher: SPRINGER, Pages: 269-269, ISSN: 0920-3206
Perbellini F, Watson SA, Thum T, et al., 2019, Adult myocardial slices a highly viable and functional platform to study cardiac biology, Publisher: WILEY, Pages: 42-43, ISSN: 0014-2972
Pitoulis F, Watson SA, Dries E, et al., 2019, Myocardial Slices - A Novel Platform for <i>In Vitro</i> Biomechanical Studies, 63rd Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 30A-30A, ISSN: 0006-3495
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- Citations: 2
King O, Kermani F, Wang B, et al., 2019, Endothelial Cell Regulation of Excitation-Contraction Coupling in Induced Pluripotent Stem Cell Derived Myocardium, 63rd Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 153A-153A, ISSN: 0006-3495
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- Citations: 2
Dubey P, Humphrey E, Majid Q, et al., 2019, Polyhydroxyalkanoates, ideal materials for cardiac regeneration, ISSN: 1526-7547
Statement of purpose: Polyhydroxyalkanoates (PHAs), a family of biodegradable and biocompatible polymers with a range of material properties and degradation rates are known to be particularly cardio-regenerative in nature1,2,3. Myocardial infarction results in the generation of scar tissue with limited or no regeneration due to the modest nature of intrinsic myocardial regenerative capability. The concept of a cardiac patch is tailored to meet the unmet medical need of cardiac regeneration where a biomaterial-based patch with/without cells would be used to induce efficient cardiac regeneration. Medium chain length PHAs (MCL-PHAs) with monomer chain length between C6-C16 are highly elastomeric in nature1,2 and have been shown to be excellent substrates for the growth and function of neonatal cardiomyocytes3. This work describes an in-depth study of the potential of MCL-PHAs for the development of functional cardiac patches laden with human pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), providing mechanical support and cell based therapy.
Fourre J, Terracciano C, Mason J, 2019, Endothelial Cells Exert Stimulus-Specific Paracrine Effects on Co-Cultured Cardiomyocytes During Inflammation, 3rd Joint Meeting of the European-Society-for-Microcirculation (ESM) and the European-Vascular-Biology-Organization (EVBO), Publisher: KARGER, Pages: 35-35, ISSN: 1018-1172
Terracciano C, 2019, Heart of the Matter Key concepts in cardiovascular science Preface, HEART OF THE MATTER: KEY CONCEPTS IN CARDIOVASCULAR SCIENCE, Editors: Terracciano, Guymer, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: VI-VII, ISBN: 978-3-030-24218-3
Pitoulis FG, Terracciano CM, 2019, Cardiac Excitation-Contraction Coupling, HEART OF THE MATTER: KEY CONCEPTS IN CARDIOVASCULAR SCIENCE, Editors: Terracciano, Guymer, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 61-75, ISBN: 978-3-030-24218-3
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