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https://www.readbyqxmd.com/read/27911047/modified-mrna-as-a-therapeutic-tool-to-induce-cardiac-regeneration-in-ischemic-heart-disease
#1
REVIEW
Yoav Hadas, Michael G Katz, Charles R Bridges, Lior Zangi
Ischemic heart disease (IHD) is a leading cause of morbidity and mortality in developed countries. Current pharmacological and interventional therapies provide significant improvement in the life quality of patient; however, they are mostly symptom-oriented and not curative. A high disease and economic burden of IHD requires the search for new therapeutic strategies to significantly improve patients' prognosis and quality of life. One of the main challenges during IHD is the massive loss of cardiomyocytes that possess minimal regenerative capacity...
December 2, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/27910042/direct-cardiac-reprogramming-as-a-novel-therapeutic-strategy-for-treatment-of-myocardial-infarction
#2
Hong Ma, Li Wang, Jiandong Liu, Li Qian
Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27906881/stem-cells-and-clinical-practice-new-advances-and-challenges-at-the-time-of-emerging-problems-with-induced-pluripotent-stem-cell-therapies
#3
Mariusz Z Ratajczak, Kamila Bujko, Wojciech Wojakowski
Humans, like other species that reproduce sexually, originate from a fertilized oocyte (zygote), which is a totipotent stem cell giving rise to an adult organism. During the process of embryogenesis, stem cells at different levels of the developmental hierarchy establish all 3 germ layers and give rise to tissue‑committed stem cells, which are responsible for rejuvenation of a given tissue or organ. The robustness of the stem cell compartment is one of the major factors that directly impact life quality as well as lifespan...
November 10, 2016: Polskie Archiwum Medycyny Wewnętrznej
https://www.readbyqxmd.com/read/27906521/modeling-the-human-scarred-heart-in-vitro-toward-new-tissue-engineered-models
#4
Janine C Deddens, Amir Hossein Sadeghi, Jesper Hjortnaes, Linda W van Laake, Marc Buijsrogge, Pieter A Doevendans, Ali Khademhosseini, Joost P G Sluijter
Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart...
December 1, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27906085/tissue-engineered-cardiac-patch-seeded-with-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-promoted-the-regeneration-of-host-cardiomyocytes-in-a-rat-model
#5
Tadahisa Sugiura, Narutoshi Hibino, Christopher K Breuer, Toshiharu Shinoka
BACKGROUND: Thousands of babies are born with congenital heart defects that require surgical repair involving a prosthetic implant. Lack of growth in prosthetic grafts is especially detrimental in pediatric surgery. Cell seeded biodegradable tissue engineered grafts are a novel solution to this problem. The purpose of the present study is to evaluate the feasibility of seeding human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) onto a biodegradable cardiac patch. METHODS: The hiPS-CMs were cultured on a biodegradable patch composed of a polyglycolic acid (PGA) and a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) for 1 week...
December 1, 2016: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/27905259/regenerative-pharmacology-recent-developments-and-future-perspectives
#6
James Koudy Williams, Karl-Erik Andersson
This review focuses on the current status of research that utilizes the application of pharmacological sciences to accelerate, optimize and characterize the development, maturation and function of bioengineered and regenerating tissues. These regenerative pharmacologic approaches have been applied to diseases of the urogenital tract, the heart, the brain, the musculoskeletal system and diabetes. Approaches have included the use of growth factors (such as VEGF and chemokines (stromal-derived factor - CXCL12) to mobilize cell to the sights of tissue loss or damage...
December 1, 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27903111/electric-stimulation-enhances-cardiac-differentiation-of-human-induced-pluripotent-stem-cells-for-myocardial-infarction-therapy
#7
Ruilian Ma, Jialiang Liang, Wei Huang, Linlin Guo, WenFeng Cai, Lei Wang, Christian Paul, Huang-Tian Yang, Ha Won Kim, Yigang Wang
AIM: Electrical stimulation (EleS) can promote cardiac differentiation, but the underlying mechanism is not well known. This study investigated the effect of EleS on cardiomyocyte (CM) differentiation of human induced pluripotent stem cells (hiPSCs) and evaluated the therapeutic effects for the treatment of myocardial infarction (MI). RESULTS: Cardiac differentiation of hiPSCs was induced with EleS after embryoid body formation. Spontaneously beating hiPSCs were observed as early at 2 days when treated with EleS as compared to control treatment...
November 30, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27886395/popdc1-bves-functions-in-the-preservation-of-cardiomyocyte-viability-while-affecting-rac1-activity-and-bnip3-expression
#8
Kliminski Vitaly, Uziel Orit, Kessler-Icekson Gania
The Popeye domain containing1, also called Bves (Popdc1/Bves), is a transmembrane protein that functions in muscle regeneration, heart rate regulation, hypoxia tolerance, and ischemia preconditioning. The expression of Popdc1/Bves is elevated in cardiomyocytes maintained in serum free defined medium. We hypothesized that Popdc1/Bves is important for cardiomyocyte survival under the stress of serum deprivation and investigated the mechanisms involved. A deficit in Popdc1/Bves, achieved by siRNA-mediated gene silencing, results in cardiomyocyte injury and death, upregulation of the pro-apoptotic protein Bcl-2/adenovirus E1B 19-kDa interacting protein3 (Bnip3), as well as reduction in Rac1-GTPase activity and in Akt phosphorylation...
November 25, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27885900/recreating-composition-structure-functionalities-of-tissues-at-nanoscale-for-regenerative-medicine
#9
Emine Alarçin, Xiaofei Guan, Sara Saheb Kashaf, Khairat Elbaradie, Huazhe Yang, Hae Lin Jang, Ali Khademhosseini
Nanotechnology offers significant potential in regenerative medicine, specifically with the ability to mimic tissue architecture at the nanoscale. In this perspective, we highlight key achievements in the nanotechnology field for successfully mimicking the composition and structure of different tissues, and the development of bio-inspired nanotechnologies and functional nanomaterials to improve tissue regeneration. Numerous nanomaterials fabricated by electrospinning, nanolithography and self-assembly have been successfully applied to regenerate bone, cartilage, muscle, blood vessel, heart and bladder tissue...
December 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27884776/inverted-orientation-improves-decellularization-of-whole-porcine-hearts
#10
Po-Feng Lee, Eric Chau, Rafael Cabello, Alvin T Yeh, Luiz C Sampaio, Andrea S Gobin, Doris A Taylor
In structurally heterogeneous organs, such as heart, it is challenging to retain extracellular matrix integrity in the thinnest regions (eg, valves) during perfusion decellularization and completely remove cellular debris from thicker areas. The high inflow rates necessary to maintain physiologic pressure can distend or damage thin tissues, but lower pressures prolong the process and increase the likelihood of contamination. We examined two novel retrograde decellularization methods for porcine hearts: inverting the heart or venting the apex to decrease inflow rate...
November 21, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27880821/inhibition-of-the-tgf%C3%AE-pathway-enhances-retinal-regeneration-in-adult-zebrafish
#11
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
https://www.readbyqxmd.com/read/27880068/human-hair-follicle-associated-pluripotent-hhap-stem-cells-differentiate-to-cardiac-muscle-cells
#12
Natsuko Tohgi, Koya Obara, Masateru Yashiro, Yuko Hamada, Nobuko Arakawa, Sumiyuki Mii, Ryoichi Aki, Robert M Hoffman, Yasuyuki Amoh
We have previously demonstrated that the nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells are located in the bulge area. HAP stem cells have been previously shown to differentiate to neurons, glial cells, keratinocytes, smooth-muscle cells, melanocytes and cardiac-muscle cells in vitro. Subsequently, we demonstrated that HAP stem cells could effect nerve and spinal cord regeneration in mouse models, differentiating to Schwann cells and neurons. In previous studies, we established an efficient protocol for the differentiation of cardiac-muscle cells from mouse HAP stem cells...
November 23, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27878328/targeting-the-hedgehog-signaling-pathway-for-cardiac-repair-and-regeneration
#13
REVIEW
Y Wang, P Lu, D Zhao, J Sheng
The hedgehog (Hh) signaling pathway is involved in the angiogenesis and development of the coronary vasculature in the embryonic heart. Recently, the Hh signal pathway has emerged as an important regulator that can increase cardiomyocyte proliferation, inhibit cardiomyocyte death and apoptosis, recruit endothelial progenitor cell (EPCs) into sites of myocardial ischemia, and direct stem cells to differentiate into cardiac muscle lineage. Experimental studies have tried to target the Hh signaling pathway for cardiac repair and regeneration...
November 22, 2016: Herz
https://www.readbyqxmd.com/read/27877076/cardiomyogenic-differentiation-of-human-dental-follicle-derived-stem-cells-by-suberoylanilide-hydroxamic-acid-and-their-in-vivo-homing-property
#14
Iel-Yong Sung, Han-Na Son, Imran Ullah, Dinesh Bharti, Ju-Mi Park, Yeong-Cheol Cho, June-Ho Byun, Young-Hoon Kang, Su-Jin Sung, Jong-Woo Kim, Gyu-Jin Rho, Bong-Wook Park
The purpose of the present study was to investigate the in vitro cardiomyogenic differentiation potential of human dental follicle-derived stem cells (DFCs) under the influence of suberoylanilide hydroxamic acid (SAHA), a member of the histone deacetylase inhibitor family, and analyze the in vivo homing capacity of induced cardiomyocytes (iCMs) when transplanted systemically. DFCs from extracted wisdom teeth showed mesenchymal stem cell (MSC) characteristics such as plate adherent growing, expression of MSC markers (CD44, CD90, and CD105), and mesenchymal lineage-specific differentiation potential...
2016: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/27875722/progenitor-cells-from-atria-ventricle-and-peripheral-blood-of-the-same-patients-exhibit-functional-differences-associated-with-cardiac-repair
#15
Parul Dixit, Hayden Donnelly, Midori Edamatsu, Ivor Galvin, Richard Bunton, Rajesh Katare
AIM: Deciding the best cell type for cardiac regeneration remains a big challenge. No studies have directly compared the functional efficacy of cardiac progenitor cells (CPCs) with extra-cardiac stem cells isolated from the same patient. METHODS AND RESULTS: We compared the functional characteristics of endothelial progenitor cells (EPCs), right atrial (RAA) CPCs and left ventricular (LV) CPCs isolated from the same patients (n=14). Within the same heart, RAA and LV CPCs exhibited marked differences in surface marker expression, with RAA CPCs exhibiting better expansion potential and migration properties...
November 19, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27875683/redox-paradox-can-hypoxia-heal-ischemic-hearts
#16
Nuno Guimarães-Camboa, Sylvia M Evans
Adult cardiomyocytes are largely thought to lack proliferative and therefore regenerative potential. Reporting in Nature, Nakada et al. (2016) find that a hypoxic regime reduces mitochondrial metabolism and promotes proliferation in adult mouse cardiomyocytes, resulting in increased regeneration following myocardial infarction. These findings suggest the potential to transform post-MI care.
November 21, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27872447/evolving-approaches-to-heart-regeneration-by-therapeutic-stimulation-of-resident-cardiomyocyte-cell-cycle
#17
Raife Dilek Turan, Galip Servet Aslan, Doğacan Yücel, Remziye Döğer, Fatih Kocabaş
Heart has long been considered a terminally differentiated organ. Recent studies, however, have suggested that there is a modest degree of cardiomyocyte (CM) turnover in adult mammalian heart, albeit not sufficient for replacement of lost CMs following cardiac injuries. Cardiac regeneration studies in various model organisms including zebrafish, newt, and more recently in neonatal mouse, have demonstrated that CM dedifferentiation and concomitant proliferation play important roles in replacement of lost CMs and restoration of cardiac contractility...
November 2016: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/27864544/investigative-nonclinical-cardiovascular-safety-and-toxicology-studies-with-bms-986094-an-ns5b-rna-dependent-rna-polymerase-inhibitor
#18
M Gill, K Horn, J Hennan, R White, D Bounous, S Clark, J R Megill, E Janovitz, M Davies, T Sanderson, M Graziano
BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials because of unexpected cardiac and renal adverse events. Investigative nonclinical studies were conducted to extend the understanding of these findings using more comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and 150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d) for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for toxicology)...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27859990/prospects-for-improving-neovascularisation-of-the-ischaemic-heart-lessons-from-development
#19
Nicola Smart
Neovascularisation of the ischaemic myocardium post-infarction is necessary to restore blood flow to vulnerable cardiomyocytes and will be indispensable for prospective regenerative strategies, to perfuse newly formed myocardium. Therapeutic attempts to enhance new vessel formation have, to date, yielded modest clinical benefits and innovative approaches are now needed. Intrinsic mechanisms are initiated by the heart in an attempt to rebuild injured vessels but these are poorly understood. Insight into the underlying mechanisms may reveal targets for therapeutically augmenting this low-level neovascular response...
November 17, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/27837563/stem-cell-banking-and-its-impact-on-cardiac-regenerative-medicine
#20
Silvana Bardelli, Marco Moccetti
Cardiovascular diseases, including heart failure, are the most frequent cause of death annually, even higher than any other pathologies. Specifically, patients who suffer from myocardial infarction may encounter adverse remodeling processes of the heart that can ultimately lead to heart failure. Prognosis of patients affected by heart failure is very poor with 5-year mortality close to 50 %. Despite the impressive progress in the clinical treatment of heart failure in recent years, heart transplantation is still required to avoid death as the result of the inexorable decline in cardiac function...
2016: Advances in Experimental Medicine and Biology
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