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https://www.readbyqxmd.com/read/29163642/potential-role-of-exosomes-in-mending-a-broken-heart-nanoshuttles-propelling-future-clinical-therapeutics-forward
#1
REVIEW
Julie A Dougherty, Muhamad Mergaye, Naresh Kumar, Chun-An Chen, Mark G Angelos, Mahmood Khan
Stem cell transplantation therapy is a promising adjunct for regenerating damaged heart tissue; however, only modest improvements in cardiac function have been observed due to poor survival of transplanted cells in the ischemic heart. Therefore, there remains an unmet need for therapies that can aid in attenuating cardiac damage. Recent studies have demonstrated that exosomes released by stem cells could serve as a potential cell-free therapeutic for cardiac repair. These exosomes/nanoshuttles, once thought to be merely a method of waste disposal, have been shown to play a crucial role in physiological functions including short- and long-distance intercellular communication...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29162747/therapeutic-effect-of-a-novel-wnt-pathway-inhibitor-on-cardiac-regeneration-after-myocardial-infarction
#2
Chunyu Zeng, Dezhong Yang, Wenbin Fu, Liangpeng Li, Xuewei Xia, Qiao Liao, Rongchuan Yue, Hongmei Chen, Xiongwen Chen, Songzhu An, Wei Eric Wang
After myocardial infarction (MI), the heart is difficult to repair because of great loss of cardiomyoctyes and lack of cardiac regeneration. Novel drug candidates that aim at reducing pathological remodeling and stimulating cardiac regeneration are highly desirable. In this study, we identified if and how a novel porcupine inhibitor CGX1321 influenced MI and cardiac regeneration. Permanent ligation of left anterior descending (LAD) coronary artery was performed in mice to induce MI injury. Cardiac function was measured by echocardiography, infarct size was examined by TTC staining...
November 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29158846/subcellular-localization-of-survivin-determines-its-function-in-cardiomyocytes
#3
Tien-Jui Tsang, Ying-Chang Hsueh, Erika I Wei, David J Lundy, Bill Cheng, You-Tzung Chen, Shoei-Shen Wang, Patrick C H Hsieh
Rationale: Reducing cardiomyocyte death and enhancing their proliferation after myocardial infarction is perhaps the single largest challenge for cardiac tissue regeneration. Survivin (SVV) is the smallest member of the inhibitor of apoptosis (IAP) family but plays two important roles; inhibiting caspase-9 activation in the intrinsic apoptosis pathway, and regulating microtubule dynamics and chromosome segregation during cell division. Genetic depletion of cardiac SVV leads to incomplete cardiomyocyte division and abnormal heart development...
2017: Theranostics
https://www.readbyqxmd.com/read/29158084/distinct-expression-patterns-of-flk1-and-flt1-in-the-coronary-vascular-system-during-development-and-after-myocardial-infarction
#4
Shota Kurotsu, Rina Osakabe, Mari Isomi, Fumiya Tamura, Taketaro Sadahiro, Naoto Muraoka, Hidenori Kojima, Sho Haginiwa, Hidenori Tani, Kaori Nara, Yoshiaki Kubota, Masatsugu Ema, Keiichi Fukuda, Takeshi Suzuki, Masaki Ieda
The coronary vascular system is critical for myocardial growth and cardiomyocyte survival. However, the molecular mechanism regulating coronary angiogenesis remains elusive. Vascular endothelial growth factor (VEGF) regulates angiogenesis by binding to the specific receptors Flk1 and Flt1, which results in different functions. Despite the importance of Flk1 and Flt1, their expression in the coronary vasculature remains largely unknown due to the lack of appropriate antibodies for immunostaining. Here, we analyzed multiple reporter mice including Flk1-GFP BAC transgenic (Tg), Flk1-LacZ knock-in, Flt1-DsRed BAC Tg, and Flk1-GFP/Flt1-DsRed double Tg animals to determine expression patterns in mouse hearts during cardiac growth and after myocardial infarction (MI)...
November 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29154163/upstairs-downstairs-spatial-regulation-of-hippo-signalling
#5
REVIEW
Alexander Fulford, Nicolas Tapon, Paulo S Ribeiro
Cellular signalling lies at the heart of every decision involved in the development and homeostasis of multicellular organisms. The Hippo pathway was discovered nearly two decades ago through seminal work in Drosophila and rapidly emerged as a crucial signalling network implicated in developmental and oncogenic growth, tissue regeneration and stem cell biology. Here, we review recent advances in the field relating to the upstream regulation of Hippo signalling and the intracellular tug-of-war that tightly controls its main target, the transcriptional co-activator Yorkie/YAP...
November 16, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29150936/the-roles-of-wnt-%C3%AE-catenin-pathway-in-tissue-development-and-regenerative-medicine
#6
REVIEW
Maryam Majidinia, Javad Aghazadeh, Rana Jahanban-Esfahlani, Bahman Yousefi
Regenerative medicine is a translational field which combines tissue engineering and molecular biology to construct spare organs or help injured or defective tissues to regenerate or restore their normal functions. This is particularly important with specific organs such as heart, central nervous system, retina or limbs which possess very limited regenerative capacity. As such, regenerative medicine has received peculiar attention in the last decade. In this regard, Wnt/β-catenin signaling pathway has been subject to intensive research, since it plays many essential roles in the regulation of the progenitor cell fate, developmental decisions, proliferation during embryonic development, and adult tissue homeostasis...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29145950/a-combination-of-allogeneic-stem-cells-promotes-cardiac-regeneration
#7
Makoto Natsumeda, Victoria Florea, Angela C Rieger, Bryon A Tompkins, Monisha N Banerjee, Samuel Golpanian, Julia Fritsch, Ana Marie Landin, Nilesh D Kashikar, Vasileios Karantalis, Viky Y Loescher, Kostas E Hatzistergos, Luiza Bagno, Cristina Sanina, Muzammil Mushtaq, Jose Rodriguez, Marcos Rosado, Ariel Wolf, Kevin Collon, Louis Vincent, Anthony J Kanelidis, Ivonne H Schulman, Raul Mitrani, Alan W Heldman, Wayne Balkan, Joshua M Hare
BACKGROUND: The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT). OBJECTIVES: This study sought to test the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions...
November 14, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29142194/transient-cardiomyocyte-fusion-regulates-cardiac-development-in-zebrafish
#8
Suphansa Sawamiphak, Zacharias Kontarakis, Alessandro Filosa, Sven Reischauer, Didier Y R Stainier
Cells can sacrifice their individuality by fusing, but the prevalence and significance of this process are poorly understood. To approach these questions, here we generate transgenic reporter lines in zebrafish to label and specifically ablate fused cells. In addition to skeletal muscle cells, the reporters label cardiomyocytes starting at an early developmental stage. Genetic mosaics generated by cell transplantation show cardiomyocytes expressing both donor- and host-derived transgenes, confirming the occurrence of fusion in larval hearts...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29131159/enhancing-the-precision-of-genetic-lineage-tracing-using-dual-recombinases
#9
Lingjuan He, Yan Li, Yi Li, Wenjuan Pu, Xiuzhen Huang, Xueying Tian, Yue Wang, Hui Zhang, Qiaozhen Liu, Libo Zhang, Huan Zhao, Juan Tang, Hongbin Ji, Dongqing Cai, Zhibo Han, Zhongchao Han, Yu Nie, Shengshou Hu, Qing-Dong Wang, Ruilin Sun, Jian Fei, Fengchao Wang, Ting Chen, Yan Yan, Hefeng Huang, William T Pu, Bin Zhou
The Cre-loxP recombination system is the most widely used technology for in vivo tracing of stem or progenitor cell lineages. The precision of this genetic system largely depends on the specificity of Cre recombinase expression in targeted stem or progenitor cells. However, Cre expression in nontargeted cell types can complicate the interpretation of lineage-tracing studies and has caused controversy in many previous studies. Here we describe a new genetic lineage tracing system that incorporates the Dre-rox recombination system to enhance the precision of conventional Cre-loxP-mediated lineage tracing...
November 13, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29121865/temporally-distinct-transcriptional-regulation-of-myocyte-dedifferentiation-and-myofiber-growth-during-muscle-regeneration
#10
Ke'ale W Louie, Alfonso Saera-Vila, Phillip E Kish, Justin A Colacino, Alon Kahana
BACKGROUND: Tissue regeneration requires a series of steps, beginning with generation of the necessary cell mass, followed by cell migration into damaged area, and ending with differentiation and integration with surrounding tissues. Temporal regulation of these steps lies at the heart of the regenerative process, yet its basis is not well understood. The ability of zebrafish to dedifferentiate mature "post-mitotic" myocytes into proliferating myoblasts that in turn regenerate lost muscle tissue provides an opportunity to probe the molecular mechanisms of regeneration...
November 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29118944/cardiac-progenitor-cells-application-in-cardiovascular-disease
#11
REVIEW
Hassan Amini, Jafar Rezaie, Armin Vosoughi, Reza Rahbarghazi, Mohammad Nouri
Stem cells (SCs) have special potency to differentiate into different types of cells, especially cardiomyocytes. In order to demonstrate the therapeutic applications of these cells, various investigations are recently being developed. Cardiac progenitor cells are endogenous cardiac SCs that found to express tyrosine kinase receptors, c-Kit and other stemness features in adult heart, contributing to the regeneration of cardiac tissue after injury. This lineage is able to efficiently trans-differentiate into different cell types such as cardiomyocytes, endothelial cells, and smooth muscle cells...
2017: Journal of Cardiovascular and Thoracic Research
https://www.readbyqxmd.com/read/29111107/mind-the-gap-current-challenges-and-future-state-of-heart-failure-care
#12
REVIEW
Michael A McDonald, Euan A Ashley, Paul W M Fedak, Nathaniel Hawkins, James L Januzzi, John J V McMurray, Victoria N Parikh, Vivek Rao, Daniyil Svystonyuk, John R Teerlink, Sean Virani
The past decade has seen many advances in the management of heart failure (HF) that have improved survival and quality of life for patients living with this condition. A number of gaps remain in our understanding of the pathophysiology of HF, and the application of emerging treatment strategies is an exciting but daunting challenge. It is possible that advances in genetic evaluation of cardiomyopathy will provide a more refined approach to characterizing HF syndromes, whereas large-scale clinical trials on the horizon should further clarify the role of novel pharmacologic agents and invasive therapies...
November 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29111100/systemic-cell-cycle-activation-is-induced-following-complex-tissue-injury-in-axolotl
#13
Kimberly Johnson, Joel Bateman, Tia DiTommaso, Alan Y Wong, Jessica L Whited
Activation of progenitor cells is crucial to promote tissue repair following injury in adult animals. In the context of successful limb regeneration following amputation, progenitor cells residing within the stump must re-enter the cell cycle to promote regrowth of the missing limb. We demonstrate that in axolotls, amputation is sufficient to induce cell-cycle activation in both the amputated limb and the intact, uninjured contralateral limb. Activated cells were found throughout all major tissue populations of the intact contralateral limb, with internal cellular populations (bone and soft tissue) the most affected...
October 27, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29093487/micrornas-promote-skeletal-muscle-differentiation-of-mesodermal-ipsc-derived-progenitors
#14
Giorgia Giacomazzi, Bryan Holvoet, Sander Trenson, Ellen Caluwé, Bojana Kravic, Hanne Grosemans, Álvaro Cortés-Calabuig, Christophe M Deroose, Danny Huylebroeck, Said Hashemolhosseini, Stefan Janssens, Elizabeth McNally, Mattia Quattrocelli, Maurilio Sampaolesi
Muscular dystrophies (MDs) are often characterized by impairment of both skeletal and cardiac muscle. Regenerative strategies for both compartments therefore constitute a therapeutic avenue. Mesodermal iPSC-derived progenitors (MiPs) can regenerate both striated muscle types simultaneously in mice. Importantly, MiP myogenic propensity is influenced by somatic lineage retention. However, it is still unknown whether human MiPs have in vivo potential. Furthermore, methods to enhance the intrinsic myogenic properties of MiPs are likely needed, given the scope and need to correct large amounts of muscle in the MDs...
November 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/29079873/regenerating-the-human-heart-direct-reprogramming-strategies-and-their-current-limitations
#15
REVIEW
Andrea Ghiroldi, Marco Piccoli, Giuseppe Ciconte, Carlo Pappone, Luigi Anastasia
Cardiovascular diseases are the leading cause of death in the Western world. Unfortunately, current therapies are often only palliative, consequently essentially making heart transplantation necessary for many patients. However, several novel therapeutic approaches in the past two decades have yielded quite encouraging results. The generation of induced pluripotent stem cells, through the forced expression of stem cell-specific transcription factors, has inspired the most promising strategies for heart regeneration by direct reprogramming of cardiac fibroblasts into functional cardiomyocytes...
October 27, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29075298/cardiac-progenitor-cells-and-the-interplay-with-their-microenvironment
#16
REVIEW
Arianna Mauretti, Sergio Spaans, Noortje A M Bax, Cecilia Sahlgren, Carlijn V C Bouten
The microenvironment plays a crucial role in the behavior of stem and progenitor cells. In the heart, cardiac progenitor cells (CPCs) reside in specific niches, characterized by key components that are altered in response to a myocardial infarction. To date, there is a lack of knowledge on these niches and on the CPC interplay with the niche components. Insight into these complex interactions and into the influence of microenvironmental factors on CPCs can be used to promote the regenerative potential of these cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29075297/stem-and-progenitor-cells-in-human-cardiopulmonary-development-and-regeneration
#17
REVIEW
Silvana Bardelli, Marco Moccetti
Already during embryonic development, the heart and the lung are thoroughly connected organs. Their interdependence allows our survival in the terrestrial environment by coupling cardiac output and gas exchange. The knowledge on developmental processes involving stem and progenitor cells is crucial to understand the onset of human cardiopulmonary diseases. The precise identification of various adult endogenous progenitors is still incomplete. Thus, caution should be exercised on newly available stem cell-based treatments until specific mechanisms of action are disclosed...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29075197/the-processes-and-mechanisms-of-cardiac-and-pulmonary-fibrosis
#18
REVIEW
Lucy A Murtha, Michael J Schuliga, Nishani S Mabotuwana, Sean A Hardy, David W Waters, Janette K Burgess, Darryl A Knight, Andrew J Boyle
Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair. However, its continued activation is highly detrimental and a common final pathway of numerous disease states including cardiovascular and respiratory disease. Worldwide, fibrotic diseases cause over 800,000 deaths per year, accounting for ~45% of total deaths...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29073604/cardiac-mesenchymal-stem-cells-proliferate-early-in-the-ischemic-heart
#19
Christian Klopsch, Anna Skorska, Marion Ludwig, Ralf Gaebel, Heiko Lemcke, Gabriela Kleiner, Martin Beyer, Brigitte Vollmar, Robert David, Gustav Steinhoff
BACKGROUND/PURPOSE: Cardiac mesenchymal stem cells (MSCs) could stimulate cell-specific regenerative mechanisms after myocardial infarction (MI) depending on spatial origin, distribution, and niche regulation. We aimed at identifying and isolating tissue-specific cardiac MSCs that could contribute to regeneration. METHODS: Following permanent ligation of the left anterior descending coronary artery in rats (n = 16), early cardiac tissues and cardiac mononuclear cells (MNCs) were analyzed by immunohistology, confocal laser scanning microscopy, and flow cytometry, respectively...
October 26, 2017: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/29071404/scalable-cardiac-differentiation-of-pluripotent-stem-cells-using-specific-growth-factors-and-small-molecules
#20
Henning Kempf, Robert Zweigerdt
The envisioned routine application of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) for therapies and industry-compliant screening approaches will require efficient and highly reproducible processes for the mass production of well-characterized CM batches.On their way toward beating CMs, hPSCs initially undergo an epithelial-to-mesenchymal transition into a primitive-streak (PS)-like population that later gives rise to all endodermal and mesodermal lineages, including cardiovascular progenies (CVPs)...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
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