Cardiac muscle is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall and the inner layer, with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix.
The endocardium is the innermost layer of tissue that lines the chambers of the heart. Its cells are embryologically and biologically similar to the endothelial cells that line blood vessels. The endocardium also provides protection to the valves and heart chambers.
T-tubules are extensions of the cell membrane that penetrate into the center of skeletal and cardiac muscle cells. With membranes that contain large concentrations of ion channels, transporters, and pumps, T-tubules permit rapid transmission of the action potential into the cell, and also play an important role in regulating cellular calcium concentration.
Cardiomyoplasty is a surgical procedure in which healthy muscle from another part of the body is wrapped around the heart to provide support for the failing heart. Most often the latissimus dorsi muscle is used for this purpose. A special pacemaker is implanted to make the skeletal muscle contract. If cardiomyoplasty is successful and increased cardiac output is achieved, it usually acts as a bridging therapy, giving time for damaged myocardium to be treated in other ways, such as remodeling by cellular therapies.
A mesoangioblast is a type of progenitor cell that is associated with vasculature walls. Mesoangioblasts exhibit many similarities to pericytes, which are found in the small vessels. Mesoangioblasts are multipotent stem cells with the potential to progress down the endothelial or mesodermal lineages. Mesoangioblasts express the critical marker of angiopoietic progenitors, KDR (FLK1). Because of these properties, mesoangioblasts are a precursor of skeletal, smooth, and cardiac muscle cells along with endothelial cells. Research has suggested their application for stem cell therapies for muscular dystrophy and cardiovascular disease.
A biological pacemaker is one or more types of cellular components that, when "implanted or injected into certain regions of the heart," produce specific electrical stimuli that mimic that of the body's natural pacemaker cells. Biological pacemakers are indicated for issues such as heart block, slow heart rate, and asynchronous heart ventricle contractions.
Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.
Protein kinase C epsilon type (PKCε) is an enzyme that in humans is encoded by the PRKCE gene. PKCε is an isoform of the large PKC family of protein kinases that play many roles in different tissues. In cardiac muscle cells, PKCε regulates muscle contraction through its actions at sarcomeric proteins, and PKCε modulates cardiac cell metabolism through its actions at mitochondria. PKCε is clinically significant in that it is a central player in cardioprotection against ischemic injury and in the development of cardiac hypertrophy.
Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the CDH2 gene. CDH2 has also been designated as CD325 . Cadherin-2 is a transmembrane protein expressed in multiple tissues and functions to mediate cell–cell adhesion. In cardiac muscle, Cadherin-2 is an integral component in adherens junctions residing at intercalated discs, which function to mechanically and electrically couple adjacent cardiomyocytes. Alterations in expression and integrity of Cadherin-2 has been observed in various forms of disease, including human dilated cardiomyopathy. Variants in CDH2 have also been identified to cause a syndromic neurodevelopmental disorder.
Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.
Atrial Light Chain-2 (ALC-2) also known as Myosin regulatory light chain 2, atrial isoform (MLC2a) is a protein that in humans is encoded by the MYL7 gene. ALC-2 expression is restricted to cardiac muscle atria in healthy individuals, where it functions to modulate cardiac development and contractility. In human diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and others, ALC-2 expression is altered.
In cardiology neocardiogenesis is the homeostatic regeneration, repair and renewal of sections of malfunctioning adult cardiovascular tissue. This includes a combination of cardiomyogenesis and angiogenesis.
Cellular cardiomyoplasty, or cell-based cardiac repair, is a new potential therapeutic modality in which progenitor cells are used to repair regions of damaged or necrotic myocardium. The ability of transplanted progenitor cells to improve function within the failing heart has been shown in experimental animal models and in some human clinical trials. In November 2011, a large group of collaborators at Minneapolis Heart Institute Foundation at Abbott Northwestern found no significant difference in left ventricular ejection fraction (LVEF) or other markers, between a group of patients treated with cellular cardiomyoplasty and a group of control patients. In this study, all patients were post MI, post percutaneous coronary intervention (PCI) and that infusion of progenitor cells occurred 2–3 weeks after intervention. In a study that is currently underway, however, more positive results were being reported: In the SCIPIO trial, patients treated with autologous cardiac stem cells post MI have been reported to be showing statistically significant increases in LVEF and reduction in infarct size over the control group at four months after implant. Positive results at the one-year mark are even more pronounced. Yet the SCIPIO trial "was recently called into question". Harvard University is "now investigating the integrity of some of the data". The Lancet recently published a non-specific ‘Expression of concern’ about the paper. Subsequently, another preclinical study also raised doubts on the rationale behind using this special kind of cell, as it was found that the special cells only have a minimal ability in generating new cardiomyocytes. Some specialists therefore now raise concerns to continue.
Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease, as well as treatment for the damage that occurs to the heart after MI. After MI, the myocardium suffers from reperfusion injury which leads to death of cardiomyocytes and detrimental remodelling of the heart, consequently reducing proper cardiac function. Transfection of cardiac myocytes with human HGF reduces ischemic reperfusion injury after MI. The benefits of HGF therapy include preventing improper remodelling of the heart and ameliorating heart dysfunction post-MI.
Human engineered cardiac tissues (hECTs) are derived by experimental manipulation of pluripotent stem cells, such as human embryonic stem cells (hESCs) and, more recently, human induced pluripotent stem cells (hiPSCs) to differentiate into human cardiomyocytes. Interest in these bioengineered cardiac tissues has risen due to their potential use in cardiovascular research and clinical therapies. These tissues provide a unique in vitro model to study cardiac physiology with a species-specific advantage over cultured animal cells in experimental studies. hECTs also have therapeutic potential for in vivo regeneration of heart muscle. hECTs provide a valuable resource to reproduce the normal development of human heart tissue, understand the development of human cardiovascular disease (CVD), and may lead to engineered tissue-based therapies for CVD patients.
A bioartificial heart is an engineered heart that contains the extracellular structure of a decellularized heart and cellular components from a different source. Such hearts are of particular interest for therapy as well as research into heart disease. The first bioartificial hearts were created in 2008 using cadaveric rat hearts. In 2014, human-sized bioartificial pig hearts were constructed. Bioartificial hearts have not been developed yet for clinical use, although the recellularization of porcine hearts with human cells opens the door to xenotransplantation.
Regeneration in humans is the regrowth of lost tissues or organs in response to injury. This is in contrast to wound healing, or partial regeneration, which involves closing up the injury site with some gradation of scar tissue. Some tissues such as skin, the vas deferens, and large organs including the liver can regrow quite readily, while others have been thought to have little or no capacity for regeneration following an injury.
Annarosa Leri is a medical doctor and former associate professor at Harvard University. Along with former professor Piero Anversa, Leri was engaged in biomedical research at Brigham and Women’s Hospital in Boston, an affiliate of Harvard Medical School. Since at least 2003 Anversa and Leri had investigated the ability of the heart to regenerate damaged cells using cardiac stem cells.
Milica Radisic is a Serbian Canadian tissue engineer, academic and researcher. She is a professor at the University of Toronto’s Institute of Biomaterials and Biomedical Engineering, and the Department of Chemical Engineering and Applied Chemistry. She co-founded TARA Biosystems and is a senior scientist at the Toronto General Hospital Research Institute.
Cardiomyocyte proliferation refers to the ability of cardiac muscle cells to progress through the cell cycle and continue to divide. Traditionally, cardiomyocytes were believed to have little to no ability to proliferate and regenerate after birth. Although other types of cells, such as gastrointestinal epithelial cells, can proliferate and differentiate throughout life, cardiac tissue contains little intrinsic ability to proliferate, as adult human cells arrest in the cell cycle. However, a recent paradigm shift has occurred. Recent research has demonstrated that human cardiomyocytes do proliferate to a small extent for the first two decades of life. Also, cardiomyocyte proliferation and regeneration has been demonstrated to occur in various neonatal mammals in response to injury in the first week of life. Current research aims to further understand the biological mechanism underlying cardiomyocyte proliferation in hopes to turn this capability back on in adults in order to combat heart disease.
