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Cardiomyocyte stem cells

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https://www.readbyqxmd.com/read/28633074/programming-cells-for-cardiac-repair
#1
REVIEW
Rocco Romagnuolo, Michael A Laflamme
Because the heart is a poorly regenerative organ, there has been considerable interest in developing novel cell-based approaches to restore lost contractile function after myocardial infarction (MI). While a wide variety of candidate cell types have been tested in animal MI models, the vast majority of clinical trials have used adult stem cell types, usually derived from bone marrow. These studies have generally yielded disappointing results, an outcome that may reflect in part the limited cardiogenic potential of the adult stem cell sources employed...
June 17, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28630169/patient-specific-drug-screening-using-a-human-induced-pluripotent-stem-cell-model-of-catecholaminergic-polymorphic-ventricular-tachycardia-type-2
#2
Leonid Maizels, Irit Huber, Gil Arbel, Anke J Tijsen, Amira Gepstein, Asaad Khoury, Lior Gepstein
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) results from autosomal recessive CASQ2 mutations, causing abnormal Ca(2+)-handling and malignant ventricular arrhythmias. We aimed to establish a patient-specific human induced pluripotent stem cell (hiPSC) model of CPVT2 and to use the generated hiPSC-derived cardiomyocytes to gain insights into patient-specific disease mechanism and pharmacotherapy. METHODS AND RESULTS: hiPSC cardiomyocytes were derived from a CPVT2 patient (D307H-CASQ2 mutation) and from healthy controls...
June 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28629100/biomaterials-and-cells-for-cardiac-tissue-engineering-current-choices
#3
REVIEW
Rusha Chaudhuri, Madhumitha Ramachandran, Pearl Moharil, Megha Harumalani, Amit K Jaiswal
The major purpose of cardiac tissue engineering is to engineer cells on scaffolds and use it as a substitute to infarcted cardiac cells. With an ever-increasing risk of cardiac diseases there is an increasing need to have a stable and sustainable approach to cure such ailments. This review provides a comprehensive update on the cell sources and biomaterials essential for cardiac tissue engineering, ensuring their biocompatibility under a variety of conditions. Cells can be obtained from allogenic or autologous sources...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28625174/quantification-of-cardiomyocyte-alignment-from-three-dimensional-3d-confocal-microscopy-of-engineered-tissue
#4
William J Kowalski, Fangping Yuan, Takeichiro Nakane, Hidetoshi Masumoto, Marc Dwenger, Fei Ye, Joseph P Tinney, Bradley B Keller
Biological tissues have complex, three-dimensional (3D) organizations of cells and matrix factors that provide the architecture necessary to meet morphogenic and functional demands. Disordered cell alignment is associated with congenital heart disease, cardiomyopathy, and neurodegenerative diseases and repairing or replacing these tissues using engineered constructs may improve regenerative capacity. However, optimizing cell alignment within engineered tissues requires quantitative 3D data on cell orientations and both efficient and validated processing algorithms...
June 19, 2017: Microscopy and Microanalysis
https://www.readbyqxmd.com/read/28624441/hsp90-inhibitor-geldanamycin-attenuates-the-cytotoxicity-of-sunitinib-in-cardiomyocytes-via-inhibition-of-the-autophagy-pathway
#5
Takayuki Kimura, Mai Uesugi, Kazuma Takase, Norimasa Miyamoto, Kohei Sawada
Sunitinib malate (sunitinib) is an orally available, multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. Although sunitinib is effective for the treatment of patients with gastrointestinal stromal tumor, advanced renal cell carcinoma, or pancreatic neuroendocrine tumor, adverse cardiac events associated with sunitinib administration have been reported. Here, we examined the effect of geldanamycin, an inhibitor of heat shock protein (Hsp) 90, on sunitinib-induced cytotoxicity in cardiomyocytes...
June 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28624390/nkx2-5-enhances-the-efficacy-of-mesenchymal-stem-cells-transplantation-in-treatment-heart-failure-in-rats
#6
Bo Deng, Jin Xin Wang, Xing Xing Hu, Peng Duan, Lin Wang, Yang Li, Qing Lei Zhu
AIMS: The aim of this study is to determine whether Nkx2.5 transfection of transplanted bone marrow mesenchymal stem cells (MSCs) improves the efficacy of treatment of adriamycin-induced heart failure in a rat model. MAIN METHODS: Nkx2.5 was transfected in MSCs by lentiviral vector transduction. The expressions of Nkx2.5 and cardiac specific genes in MSCs and Nkx2.5 transfected mesenchymal stem cells (MSCs-Nkx2.5) were analyzed with quantitative real-time PCR and Western blot in vitro...
June 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28624223/evaluation-of-mybpc3-trans-splicing-and-gene-replacement-as-therapeutic-options-in-human-ipsc-derived-cardiomyocytes
#7
Maksymilian Prondzynski, Elisabeth Krämer, Sandra D Laufer, Aya Shibamiya, Ole Pless, Frederik Flenner, Oliver J Müller, Julia Münch, Charles Redwood, Arne Hansen, Monica Patten, Thomas Eschenhagen, Giulia Mearini, Lucie Carrier
Gene therapy is a promising option for severe forms of genetic diseases. We previously provided evidence for the feasibility of trans-splicing, exon skipping, and gene replacement in a mouse model of hypertrophic cardiomyopathy (HCM) carrying a mutation in MYBPC3, encoding cardiac myosin-binding protein C (cMyBP-C). Here we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from an HCM patient carrying a heterozygous c.1358-1359insC MYBPC3 mutation and from a healthy donor. HCM hiPSC-CMs exhibited ∼50% lower MYBPC3 mRNA and cMyBP-C protein levels than control, no truncated cMyBP-C, larger cell size, and altered gene expression, thus reproducing human HCM features...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623610/a-singular-role-of-ik1-promoting-the-development-of-cardiac-automaticity-during-cardiomyocyte-differentiation-by-ik1-induced-activation-of-pacemaker-current
#8
Yu Sun, Valeriy Timofeyev, Adrienne Dennis, Emre Bektik, Xiaoping Wan, Kenneth R Laurita, Isabelle Deschênes, Ronald A Li, Ji-Dong Fu
The inward rectifier potassium current (IK1) is generally thought to suppress cardiac automaticity by hyperpolarizing membrane potential (MP). We recently observed that IK1 could promote the spontaneously-firing automaticity induced by upregulation of pacemaker funny current (If) in adult ventricular cardiomyocytes (CMs). However, the intriguing ability of IK1 to activate If and thereby promote automaticity has not been explored. In this study, we combined mathematical and experimental assays and found that only IK1 and If, at a proper-ratio of densities, were sufficient to generate rhythmic MP-oscillations even in unexcitable cells (i...
June 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28619993/low-extracellular-potassium-prolongs-repolarization-and-evokes-early-afterdepolarization-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#9
Jukka Kuusela, Kim Larsson, Disheet Shah, Chandra Prajapati, Katriina Aalto-Setälä
Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K(+) Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K(+) concentration ([K(+)]Ex) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1 The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28615142/overexpression-of-kcnj2-in-induced-pluripotent-stem-cell-derived-cardiomyocytes-for-the-assessment-of-qt-prolonging-drugs
#10
Min Li, Yasunari Kanda, Takashi Ashihara, Tetsuo Sasano, Yuji Nakai, Masami Kodama, Erina Hayashi, Yuko Sekino, Tetsushi Furukawa, Junko Kurokawa
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes hold great potentials to predict pro-arrhythmic risks in preclinical cardiac safety screening, although the hiPSC cardiomyocytes exhibit rather immature functional and structural characteristics, including spontaneous activity. Our physiological characterization and mathematical simulation showed that low expression of the inward-rectifier potassium (IK1) channel is a determinant of spontaneous activity. To understand impact of the low IK1 expression on the pharmacological properties, we tested if transduction of hiPSC-derived cardiomyocytes with KCNJ2, which encodes the IK1 channel, alters pharmacological response to cardiac repolarization processes...
May 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28605368/murine-short-axis-ventricular-heart-slices-for-electrophysiological-studies
#11
Gabriel Peinkofer, Juergen Hescheler, Marcel Halbach
Murine cardiomyocytes have been extensively used for in vitro studies of cardiac physiology and new therapeutic strategies. However, multicellular preparations of dissociated cardiomyocytes are not representative of the complex in vivo structure of cardiomyocytes, non-myocytes and extracellular matrix, which influences both mechanical and electrophysiological properties of the heart. Here we describe a technique to prepare viable ventricular slices of adult mouse hearts with a preserved in vivo like tissue structure, and demonstrate their suitability for electrophysiological recordings...
June 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28604846/identification-of-active-components-in-yixinshu-capsule-with-protective-effects-against-myocardial-dysfunction-on-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-by-an-integrative-approach
#12
Minyu Zhang, Hongwei Wu, Feifei Guo, Yangyang Yu, Junying Wei, Ya Geng, Shifeng Wang, Shiyou Li, Hongjun Yang
Traditional Chinese medicine (TCM) preparations have significant effects on some refractory diseases; however, these compositions are complex and their mechanisms are unknown. Identification of the active components in these preparations is essential. The mortality rate for heart failure (HF) has been increasing in recent years, and myocardial dysfunction (MD) has been proved to be the pathological basis of HF. Yixinshu Capsule (YXSC) is a multi-component oral drug with therapeutic effects on HF. However, the key active components are still unclear...
June 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28603177/recent-progress-using-pluripotent-stem-cells-for-cardiac-regenerative-therapy
#13
Hajime Ichimura, Yuji Shiba
Pluripotent stem cells (PSCs) have gained interest for cell-based regenerative therapies because of their capacity to differentiate into most somatic cell types, including cardiomyocytes. Remarkable progress in the generation of PSC-derived cardiomyocytes has been made in this decade, and recent preclinical transplantation studies using various animal models have provided proof-of-principle for their use in heart regeneration. However, several obstacles preclude their effective and safe clinical application for cardiac repair, including the need for approaches that prevent tumorigenesis, arrhythmogenesis, and immune rejection...
June 10, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28602846/granulocyte-colony-stimulating-factor-for-the-treatment-of-cardiovascular-diseases-an-update-with-a-critical-appraisal
#14
REVIEW
Domenico D'Amario, Antonio Maria Leone, Josip Anđelo Borovac, Francesco Cannata, Andrea Siracusano, Giampaolo Niccoli, Filippo Crea
Heart failure and acute myocardial infarction are conditions that are associated with high morbidity and mortality. Significant dysfunction of the heart muscle can occur as the consequence of end-stage chronic cardiovascular diseases or acute ischemic events that are marked by large infarction area and significant tissue necrosis. Despite the remarkable improvement of conventional treatments, a substantial proportion of patients still develops severe heart failure that can only be resolved by heart transplantation or mechanical device implantation...
June 7, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28600799/extracellular-matrix-protein-laminin-enhances-mesenchymal-stem-cell-msc-paracrine-function-through-%C3%AE-v%C3%AE-3-cd61-integrin-to-reduce-cardiomyocyte-apoptosis
#15
Kai-Yen Peng, Yuan-Hung Liu, Yu-Wei Li, Betty Linju Yen, Men-Luh Yen
Myocardial ischaemia (MI) results in extensive cardiomyocyte death and reactive oxygen species (ROS)-induced damage in an organ with little or no regenerative capacity. Although the use of adult bone marrow mesenchymal stem cells (BMMSCs) has been proposed as a treatment option, the high cell numbers required for clinical use are difficult to achieve with this source of MSCs, and animal studies have produced inconsistent data. We recently demonstrated in small and large animal models of acute MI that the application of human term placenta-derived multipotent cells (PDMCs), a foetal-stage MSC, resulted in reversal of cardiac injury with therapeutic efficacy...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28600129/angiogenic-peptide-nanofibers-repair-cardiac-tissue-defect-after-myocardial-infarction
#16
Abdul Jalil Rufaihah, I Ceren Yasa, Vaibavi Srirangam Ramanujam, Suganya Cheyyatraivendran Arularasu, Theo Kofidis, Mustafa O Guler, Ayse B Tekinay
Myocardial infarction remains one of the top leading causes of death in the world and the damage sustained in the heart eventually develops into heart failure. Limited conventional treatment options due to the inability of the myocardium to regenerate after injury and shortage of organ donors require the development of alternative therapies to repair the damaged myocardium. Current efforts in repairing damage after myocardial infarction concentrates on using biologically derived molecules such as growth factors or stem cells, which carry risks of serious side effects including the formation of teratomas...
June 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28596337/cardiac-regeneration-strategies-staying-young-at-heart
#17
REVIEW
Eldad Tzahor, Kenneth D Poss
The human heart is continually operating as a muscular pump, contracting, on average, 80 times per minute to propel 8000 liters of blood through body tissues each day. Whereas damaged skeletal muscle has a profound capacity to regenerate, heart muscle, at least in mammals, has poor regenerative potential. This deficiency is attributable to the lack of resident cardiac stem cells, combined with roadblocks that limit adult cardiomyocytes from entering the cell cycle and completing division. Insights for regeneration have recently emerged from studies of animals with an elevated innate capacity for regeneration, the innovation of stem cell and reprogramming technologies, and a clearer understanding of the cardiomyocyte genetic program and key extrinsic signals...
June 9, 2017: Science
https://www.readbyqxmd.com/read/28592841/lipopolysaccharides-induced-inflammatory-responses-and-electrophysiological-dysfunctions-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#18
Gökhan Yücel, Zhihan Zhao, Ibrahim El-Battrawy, Huan Lan, Siegfried Lang, Xin Li, Fanis Buljubasic, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Ursula Ravens, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591641/cardiac-stem-cells-for-myocardial-regeneration-promising-but-not-ready-for-prime-time
#19
REVIEW
Joshua Lader, Maxine Stachel, Lei Bu
Remarkable strides have been made in the treatment of ischemic heart disease in decades. As the initial loss of cardiomyocytes associated with myocardial infarction serves as an impetus for myocardial remodeling, the ability to replace these cells with healthy counterparts would represent an effective treatment for many forms of cardiovascular disease. The discovery of cardiac stem cells (that can differentiate into multiple lineages) highlighted the possibility for development of cell-based therapeutics to achieve this ultimate goal...
June 4, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28587156/differential-sarcomere-and-electrophysiological-maturation-of-human-ipsc-derived-cardiac-myocytes-in-monolayer-vs-aggregation-based-differentiation-protocols
#20
Dorota Jeziorowska, Vincent Fontaine, Charlène Jouve, Eric Villard, Sébastien Dussaud, David Akbar, Valérie Letang, Pauline Cervello, Jean-Michiel Itier, Marie-Pierre Pruniaux, Jean-Sébastien Hulot
Human induced pluripotent stem cells (iPSCs) represent a powerful human model to study cardiac disease in vitro, notably channelopathies and sarcomeric cardiomyopathies. Different protocols for cardiac differentiation of iPSCs have been proposed either based on embroid body formation (3D) or, more recently, on monolayer culture (2D). We performed a direct comparison of the characteristics of the derived cardiomyocytes (iPSC-CMs) on day 27 ± 2 of differentiation between 3D and 2D differentiation protocols with two different Wnt-inhibitors were compared: IWR1 (inhibitor of Wnt response) or IWP2 (inhibitor of Wnt production)...
June 1, 2017: International Journal of Molecular Sciences
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