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International Journal of Molecular... Aug 2021Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used for disease modeling and drug cardiotoxicity screening. To this end, we...
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used for disease modeling and drug cardiotoxicity screening. To this end, we recently developed human cardiac organoids (hCOs) for modeling human myocardium. Here, we perform a transcriptomic analysis of various in vitro hiPSC-CM platforms (2D iPSC-CM, 3D iPSC-CM and hCOs) to deduce the strengths and limitations of these in vitro models. We further compared iPSC-CM models to human myocardium samples. Our data show that the 3D in vitro environment of 3D hiPSC-CMs and hCOs stimulates the expression of genes associated with tissue formation. The hCOs demonstrated diverse physiologically relevant cellular functions compared to the hiPSC-CM only models. Including other cardiac cell types within hCOs led to more transcriptomic similarities to adult myocardium. hCOs lack matured cardiomyocytes and immune cells, which limits a complete replication of human adult myocardium. In conclusion, 3D hCOs are transcriptomically similar to myocardium, and future developments of engineered 3D cardiac models would benefit from diversifying cell populations, especially immune cells.
Topics: Adult; Cells, Cultured; Humans; Induced Pluripotent Stem Cells; Myocardium; Myocytes, Cardiac; Organoids; Transcriptome
PubMed: 34445185
DOI: 10.3390/ijms22168482 -
Experimental & Molecular Medicine Mar 2010In developed countries, in which people have nutrient-rich diets, convenient environments, and access to numerous medications, the disease paradigm has changed.... (Review)
Review
In developed countries, in which people have nutrient-rich diets, convenient environments, and access to numerous medications, the disease paradigm has changed. Nowadays, heart failure is one of the major causes of death. In spite of this, the therapeutic efficacies of medications are generally unsatisfactory. Although whole heart transplantation is ideal for younger patients with heart failure, many patients are deemed to be unsuitable for this type of surgery due to complications and/or age. The need for therapeutic alternatives to heart transplantation is great. Regenerative therapy is a strong option. For this purpose, several cell sources have been investigated, including intrinsic adult stem or progenitor cells and extrinsic pluripotent stem cells. Most intrinsic stem cells seem to contribute to a regenerative environment via paracrine factors and/or angiogenesis, whereas extrinsic pluripotent stem cells are unlimited sources of cardiomyocytes. In this review, we summarize the various strategies for using regenerative cardiomyocytes including our recent progressions: non-genetic approaches for the purification of cardiomyocytes and efficient transplantation. We expect that use of intrinsic and extrinsic stem cells in combination will enhance therapeutic effectiveness.
Topics: Animals; Embryonic Stem Cells; Humans; Myocardium; Myocytes, Cardiac; Regeneration; Stem Cell Transplantation; Tissue Engineering
PubMed: 20164677
DOI: 10.3858/emm.2010.42.3.022 -
Journal of the American Medical... Jan 1960
Topics: Heart; Myocardium
PubMed: 13800771
DOI: 10.1001/jama.1960.03020050030009 -
Advances in Experimental Medicine and... 2022The role of parvovirus B19 (PVB19) in the pathogenesis of idiopathic dilated cardiomyopathy (DCM) remains poorly understood. Therefore, we have measured the levels of...
The role of parvovirus B19 (PVB19) in the pathogenesis of idiopathic dilated cardiomyopathy (DCM) remains poorly understood. Therefore, we have measured the levels of inflammation, fibrosis, apoptosis, and necrosis in endomyocardial biopsies (EMBs) and sera of nonischemic PVB19-positive (n = 14) and PVB19-negative (n = 18) DCM patients. Chronic persistence of PVB19 in myocardium did not induce significant infiltration of T cells (CD3 and CD45Ro) and macrophages (CD68), and did not secrete TNFα, IL-6, and CRB. The fibrosis in PVB19-positive EMBs was also lower compared to the virus-negative ones, while ECM degrading matrix metalloproteinase MMP1 and gelatinase MMP2 were significantly (by twofold) upregulated. In addition, there was no activation of neither apoptotic nor necrotic pathways. However, levels of antiapoptotic mitochondrial Bcl-2 and heat shock protein 60 (Hsp60) in PVB19-positive biopsies were almost threefold lower than in PVB19-negative ones revealing impairment of mitochondria. Altogether, data indicate that persistence of PVB19 in myocardiums of nonischemic DCM patients can cause myocardial ECM remodeling through the MMPs, such as MMP1 and MMP2, and mitochondrial impairment. The correlative analysis of measured biomarkers suggested likely further activation of apoptotic cell death pathways rather than fibrosis. Data also suggest that antiviral therapy could be beneficial for PVB19-positive DCM patients by managing further pathological myocardial remodeling.
Topics: Cardiomyopathy, Dilated; Fibrosis; Humans; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Myocardium; Necrosis; Parvovirus B19, Human
PubMed: 35025080
DOI: 10.1007/5584_2021_702 -
Biulleten' Eksperimental'noi Biologii I... May 1995
Review
Topics: Animals; Cell Division; Genome; Heart; Humans; Myocardium; Polyploidy
PubMed: 7579231
DOI: No ID Found -
Biochimica Et Biophysica Acta Oct 2016It is well documented that fatty acids serve as the primary fuel substrate for the contracting myocardium. However, extensive research has identified significant changes... (Review)
Review
It is well documented that fatty acids serve as the primary fuel substrate for the contracting myocardium. However, extensive research has identified significant changes in the myocardial oxidation of fatty acids during acute or chronic cardiac stress. As a result, the redistribution or partitioning of fatty acids due to metabolic derangements could have biological implications. Fatty acids can be stored as triacylglycerols, serve as critical components for biosynthesis of phospholipid membranes, and form the potent signaling molecules, diacylglycerol and ceramides. Therefore, the contribution of lipid metabolism to health and disease is more intricate than a balance of uptake and oxidation. In this review, the available data regarding alterations that occur in endogenous cardiac lipid pathways during the pathological stressors of ischemia-reperfusion and pathological hypertrophy/heart failure are highlighted. In addition, changes in endogenous lipids observed in exercise training models are presented for comparison. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk.
Topics: Animals; Cardiovascular Diseases; Fatty Acids; Humans; Lipid Metabolism; Models, Animal; Myocardium; Stress, Physiological
PubMed: 27040509
DOI: 10.1016/j.bbalip.2016.03.028 -
International Journal of Cardiology Aug 2024
Topics: Humans; Fibroblasts; Myocardium
PubMed: 38754585
DOI: 10.1016/j.ijcard.2024.132162 -
Likars'ka Sprava 2007Cardio-vascular diseases and acute coronary syndrome (ACS) in the first place play the first role in the structure of diseases and mortality of world population.... (Review)
Review
Cardio-vascular diseases and acute coronary syndrome (ACS) in the first place play the first role in the structure of diseases and mortality of world population. Effective method of diagnostics of ACS consists in detecting early and late biomarkers of myocardium necrosis. The article presents characteristics of such biomarkers indices as myoglobin, cardiotroponins, MB-fractions of creatine phosphokinase, cardio-form of protein, lactate dehydrogenase, aspartate aminotransferase. The authors described in the artcile diseases which are accomponied with increase in the level of cardiotroponins.
Topics: Acute Coronary Syndrome; Biomarkers; Humans; Myocardium; Necrosis; Time Factors
PubMed: 18712092
DOI: No ID Found -
Science Translational Medicine Mar 2017Structural changes in the developing heart may influence the limited regenerative capacity of the adult heart. We examine how the workload exerted on the adult mammalian... (Review)
Review
Structural changes in the developing heart may influence the limited regenerative capacity of the adult heart. We examine how the workload exerted on the adult mammalian heart may limit regenerative capability and discuss recent therapies that demonstrate beneficial effects through unloading the heart.
Topics: Animals; Cell Shape; Heart; Humans; Myocardium; Regeneration
PubMed: 28356512
DOI: 10.1126/scitranslmed.aad9019 -
Biological & Pharmaceutical Bulletin 2015Loss of cardiac myocytes plays a critical role in the pathogenesis of cardiovascular disorders. A decrease in the number of cardiac myocytes in cardiac diseases results... (Review)
Review
Loss of cardiac myocytes plays a critical role in the pathogenesis of cardiovascular disorders. A decrease in the number of cardiac myocytes in cardiac diseases results in sustained, irreversible contractile failure of myocardium. Therefore prevention of cardiac cell death is a potential therapeutic strategy for various heart diseases. It is well accepted that three types of phenomena such as apoptosis, necrosis, and autophagy may be involved in myocardial cell death. Apoptosis is a highly regulated process that is promoted via death receptor pathway in the plasma membrane or via mitochondrial pathway. Necrosis is induced via mitochondrial swelling, cell rupture, and subsequent inflammation. Autophagy is a cell survival mechanism that involves degradation and recycling of cytoplasmic components. As compared with the other two mechanisms, autophagy may mediate cell death under specific conditions. These three types of cell death in the myocardium are discussed in this article.
Topics: Apoptosis; Autophagy; Cell Death; Cell Survival; Heart Diseases; Humans; Myocardium; Myocytes, Cardiac; Necrosis
PubMed: 26235571
DOI: 10.1248/bpb.b15-00288