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https://www.readbyqxmd.com/read/28729726/heart-regeneration-and-repair-after-myocardial-infarction-translational-opportunities-for-novel-therapeutics
#1
REVIEW
Thomas J Cahill, Robin P Choudhury, Paul R Riley
Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix...
July 21, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28729454/multimodal-regulation-of-cardiac-myocyte-proliferation
#2
REVIEW
Xuejun Yuan, Thomas Braun
Efficient cardiac regeneration is closely associated with the ability of cardiac myocytes to proliferate. Fetal or neonatal mouse hearts containing proliferating cardiac myocytes regenerate even extensive injuries, whereas adult hearts containing mostly post-mitotic cardiac myocytes have lost this ability. The same correlation is seen in some homoiotherm species such as teleost fish and urodelian amphibians leading to the hypothesis that cardiac myocyte proliferation is a major driver of heart regeneration...
July 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28718622/graphene-sheet-induced-global-maturation-of-cardiomyocytes-derived-from-human-induced-pluripotent-stem-cells
#3
Jiaxian Wang, Chang Cui, Haiyan Nan, Yuanfang Yu, Yini Xiao, Ellen Poon, Gang Yang, Xijie Wang, Chenchen Wang, Lingsong Li, Kenneth Richard Boheler, Xu Ma, Xin Cheng, Zhenhua Ni, Minglong Chen
Human induced pluripotent stem cells (hiPSCs) can proliferate infinitely. Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling, drug screening and regenerative medicine. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) display a low degree of maturation and fetal-like properties. Current in vitro differentiation methods do not mimic the structural, mechanical, and physiological properties of the cardiogenesis niche. Recently, we present an efficient cardiac maturation platform that combines hiPSCs monolayer cardiac differentiation with graphene substrate which is a biocompatible and superconductive material...
July 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28715377/creation-of-cardiac-tissue-exhibiting-mechanical-integration-of-spheroids-using-3d-bioprinting
#4
Chin Siang Ong, Takuma Fukunishi, Andrew Nashed, Adriana Blazeski, Huaitao Zhang, Samantha Hardy, Deborah DiSilvestre, Luca Vricella, John Conte, Leslie Tung, Gordon Tomaselli, Narutoshi Hibino
This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted and mixed at desired cell ratios. They are co-cultured in individual wells in ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These spheroids are then picked up by a nozzle using vacuum suction and assembled on a needle array using a 3D bioprinter. The spheroids are then allowed to fuse on the needle array...
July 2, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28707671/cardiomyocyte-proliferation-remove-brakes-and-push-accelerators
#5
Lingjuan He, Bin Zhou
Adult mammalian hearts cannot repair by themselves after injury due to limited proliferation of cardiomyocytes; removal of cell cycle blocker and/or addition of drugs that boost proliferation of cardiomyocytes provide potential means to cardiac regeneration. Three publications that appeared recently in Nature and Cell Research now provide new hope to the treatment of heart injuries.
July 14, 2017: Cell Research
https://www.readbyqxmd.com/read/28697334/heart-regeneration-4-0-matrix-medicine
#6
Elif Eroglu, Kenneth R Chien
The heart has a markedly limited capacity for regeneration. Reporting in Nature, Bassat et al. (2017) and Morikawa et al. (2017) have uncovered a new mechanism of Yap inhibition by the dystrophin glycoprotein complex (DGC) that is released by the extracellular matrix protein Agrin in order to promote cardiac regeneration.
July 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28690194/examining-a-role-for-pkg-i%C3%AE-oxidation-in-the-pathogenesis-of-cardiovascular-dysfunction-during-diet-induced-obesity
#7
Olena Rudyk, Philip Eaton
BACKGROUND: Protein kinase G (PKG) Iα is the end-effector kinase that mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to maintain blood pressure during health. A hallmark of cardiovascular disease is attenuated NO production, which in part is caused by NO Synthase (NOS) uncoupling, which in turn increases oxidative stress because of superoxide generation. NOS uncoupling promotes PKG Iα oxidation to the interprotein disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively regulates oxidation of the kinase to its active disulfide dimeric state...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28684664/mesenchymal-stem-stromal-cell-derived-extracellular-vesicles-and-their-potential-as-novel-immunomodulatory-therapeutic-agents
#8
REVIEW
Verena Börger, Michel Bremer, Rita Ferrer-Tur, Lena Gockeln, Oumaima Stambouli, Amina Becic, Bernd Giebel
Extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as mediators of a newly-discovered intercellular communication system. They are essential signaling mediators in various physiological and pathophysiological processes. Depending on their origin, they fulfill different functions. EVs of mesenchymal stem/stromal cells (MSCs) have been found to promote comparable therapeutic activities as MSCs themselves. In a variety of in vivo models, it has been observed that they suppress pro-inflammatory processes and reduce oxidative stress and fibrosis...
July 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28684531/cardiomyocyte-regeneration-a-consensus-statement
#9
Thomas Eschenhagen, Roberto Bolli, Thomas Braun, Loren J Field, Bernd K Fleischmann, Jonas Frisén, Mauro Giacca, Joshua M Hare, Steven R Houser, Richard T Lee, Eduardo Marbán, James F Martin, Jeffery D Molkentin, Charles E Murry, Paul R Riley, Pilar Ruiz-Lozano, Hesham A Sadek, Mark A Sussman, Joseph A Hill
Cell therapy is an exciting option for repairing the injured heart, one which has attracted considerable interest over the past 15 years. Consensus exists that the injection/infusion or tissue-based implantation of various cell types may exert therapeutic effects, and there is general agreement that additional molecular, translational and clinical studies are required to define the optimal cell source, method of delivery, and underlying mechanism(s) of action.One of the remaining questions in this field pertains to cardiomyocyte turnover under normal and diseased conditions and its contribution to the beneficial effects of cell therapy...
July 6, 2017: Circulation
https://www.readbyqxmd.com/read/28674697/cell-free-vascular-grafts-recent-developments-and-clinical-potential
#10
Sindhu Row, Ana Santandreu, Daniel D Swartz, Stelios T Andreadis
Recent advances in vascular tissue engineering have led to the development of cell-free grafts that are available off-the-shelf for on demand surgery. Challenges associated with cell-based technologies including cell sourcing, cell expansion and long-term bioreactor culture motivated the development of completely cell-free vascular grafts. These are based on decellularized arteries, decellularized cultured cell-based tissue engineered grafts or biomaterials functionalized with biological signals that promote in situ tissue regeneration...
March 2017: Technology
https://www.readbyqxmd.com/read/28670973/cellular-mechanisms-underlying-cardiac-engraftment-of-stem-cells
#11
Pushpinder Kanda, Darryl R Davis
Over the past decade, it has become clear that long-term engraftment of any ex vivo expanded cell product transplanted into injured myocardium is modest and all therapeutic regeneration is mediated by stimulation of endogenous repair rather than differentiation of transplanted cells into working myocardium. Given that increasing the retention of transplanted cells boosts myocardial function, focus on the fundamental mechanisms limiting retention and survival of transplanted cells may enable strategies to help to restore normal cardiac function...
July 3, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28670398/microrna-1825-induces-proliferation-of-adult-cardiomyocytes-and-promotes-cardiac-regeneration-post-ischemic-injury
#12
Raghav Pandey, Sebastian Velasquez, Shazia Durrani, Min Jiang, Michelle Neiman, Jeffrey S Crocker, Joshua B Benoit, Jack Rubinstein, Arghya Paul, Rafeeq Ph Ahmed
In mammals, proliferative capacity of cardiomyocytes is lost soon after birth, while zebrafish and other lower organisms like newts are known to regenerate injured hearts even at an adult age. Here, we show that miR-1825 can induce robust proliferation of adult rat cardiomyocytes and can improve cardiac function in-vivo post myocardial infarction. Rat adult cardiomyocytes transfected with miR-1825 showed a significant increase in DNA synthesis, mitosis, cytokinesis, and an increase in cell number when compared to cel-miR-67 transfected control...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28667562/the-innate-immune-response-in-myocardial-infarction-repair-and-regeneration
#13
Rebecca Gentek, Guillaume Hoeffel
Following myocardial infarction (MI), resident innate immune cells such as macrophages, innate lymphoid cells, and mast cells rapidly coordinate their function to contain inflammation by removing dying cells and promoting cardiomyocyte replenishment. To sustain local tissue repair functions, hematopoietic progenitors are mobilized from the bone marrow to the spleen to generate subsequent myeloid cells such as monocytes and neutrophils, which are rapidly recruited at the site of MI. A finely tuned balance between local adaptation and recruitment controls the overall outcome of the cardiac tissue regeneration versus repair and scar formation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28667270/fam64a-is-a-novel-cell-cycle-promoter-of-hypoxic-fetal-cardiomyocytes-in-mice
#14
Ken Hashimoto, Aya Kodama, Takeshi Honda, Akira Hanashima, Yoshihiro Ujihara, Takashi Murayama, Shin-Ichiro Nishimatsu, Satoshi Mohri
Fetal cardiomyocytes actively proliferate to form the primitive heart in utero in mammals, but they stop dividing shortly after birth. The identification of essential molecules maintaining this active cardiomyocyte proliferation is indispensable for potential adult heart regeneration. A recent study has shown that this proliferation depends on a low fetal oxygen condition before the onset of breathing at birth. We have established an isolation protocol for mouse fetal cardiomyocytes, performed under strict low oxygen conditions to mimic the intrauterine environment, that gives the highest proliferative activities thus far reported...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28659386/fate-predetermination-of-cardiac-myocytes-during-zebrafish-heart-regeneration
#15
Isil Tekeli, Anna Garcia-Puig, Mario Notari, Cristina García-Pastor, Isabelle Aujard, Ludovic Jullien, Angel Raya
Adult zebrafish have the remarkable ability to regenerate their heart upon injury, a process that involves limited dedifferentiation and proliferation of spared cardiomyocytes (CMs), and migration of their progeny. During regeneration, proliferating CMs are detected throughout the myocardium, including areas distant to the injury site, but whether all of them are able to contribute to the regenerated tissue remains unknown. Here, we developed a CM-specific, photoinducible genetic labelling system, and show that CMs labelled in embryonic hearts survive and contribute to all three (primordial, trabecular and cortical) layers of the adult zebrafish heart...
June 2017: Open Biology
https://www.readbyqxmd.com/read/28659307/passive-regeneration-of-glutathione-glutathione-reductase-regulation-from-the-freeze-tolerant-north-american-wood-frog-rana-sylvatica
#16
Neal J Dawson, Kenneth B Storey
Wood frogs inhabit a broad range across North America, extending from the southern tip of the Appalachian Mountains to the northern boreal forest. Remarkably they can survive the winter in a frozen state, where as much as 70% of their body water is converted into ice. During the frozen state, their hearts cease to pump blood, causing their cells to experience ischemia which can dramatically increase the production of reactive oxygen species produced within the cell. To overcome this, wood frogs have elevated levels of glutathione, a primary antioxidant...
June 28, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28655642/the-use-and-abuse-of-cre-lox-recombination-to-identify-adult-cardiomyocyte-renewal-rate-and-origin
#17
REVIEW
Iolanda Aquila, Fabiola Marino, Eleonora Cianflone, Pina Marotta, Michele Torella, Vincenzo Mollace, Ciro Indolfi, Bernardo Nadal-Ginard, Daniele Torella
The adult mammalian heart, including the human, is unable to regenerate segmental losses after myocardial infarction. This evidence has been widely and repeatedly used up-to-today to suggest that the myocardium, contrary to most adult tissues, lacks an endogenous stem cell population or more specifically a bona-fide cardiomyocyte-generating progenitor cell of biological significance. In the last 15 years, however, the field has slowly evolved from the dogma that no new cardiomyocytes were produced from shortly after birth to the present consensus that new cardiomyocytes are formed throughout lifespan...
June 24, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28655578/unusual-tissue-distribution-of-carcinin-an-antibacterial-crustin-in-the-crab-carcinus-maenas-reveals-its-multi-functionality
#18
Suzanne Suleiman, Valerie J Smith, Elisabeth A Dyrynda
Crustins are whey acidic four-disulphide core (WFDSC) domain-containing proteins in decapods that are widely regarded as antimicrobial agents that contribute to host defence. Whilst there have been many analyses of crustin gene expression in tissues, few studies have been made of the distribution of the natural proteins. Here we report an immunostaining investigation of carcinin, a native crustin from Carcinus maenas, in the body organs. The results show that the protein is largely confined to the haemocytes with only a weak signal detected in the heart, hepatopancreas and midgut caecum where it is restricted to the outer surfaces...
June 24, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28650345/preexisting-endothelial-cells-mediate-cardiac-neovascularization-after-injury
#19
Lingjuan He, Xiuzhen Huang, Onur Kanisicak, Yi Li, Yue Wang, Yan Li, Wenjuan Pu, Qiaozhen Liu, Hui Zhang, Xueying Tian, Huan Zhao, Xiuxiu Liu, Shaohua Zhang, Yu Nie, Shengshou Hu, Xiang Miao, Qing-Dong Wang, Fengchao Wang, Ting Chen, Qingbo Xu, Kathy O Lui, Jeffery D Molkentin, Bin Zhou
The mechanisms that promote the generation of new coronary vasculature during cardiac homeostasis and after injury remain a fundamental and clinically important area of study in the cardiovascular field. Recently, it was reported that mesenchymal-to-endothelial transition (MEndoT) contributes to substantial numbers of coronary endothelial cells after myocardial infarction. Therefore, the MEndoT has been proposed as a paradigm mediating neovascularization and is considered a promising therapeutic target in cardiac regeneration...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28650344/the-relationship-between-cardiac-endothelium-and-fibroblasts-it-s-complicated
#20
Ravi Karra, Agoston O Walter, Sean M Wu
Coronary revascularization is an effective means of treating ischemic heart disease; however, current therapeutic revascularization strategies are limited to large caliber vessels. Because the mammalian heart scars following cardiac injury, recent work showing that cardiac fibroblasts can transdifferentiate into new coronary endothelium raises a new and exciting approach to promoting endogenous revascularization following cardiac injury. In this issue of the JCI, He et al. report on their employment of a battery of lineage-tracing tools to address the developmental origins of fibroblasts that give rise to new endothelial cells...
June 26, 2017: Journal of Clinical Investigation
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