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Myocardial regeneration

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https://www.readbyqxmd.com/read/28235633/cell-therapy-for-heart-disease-after-15-years-unmet-expectations
#1
REVIEW
Patrizia Nigro, Beatrice Bassetti, Laura Cavallotti, Valentina Catto, Corrado Carbucicchio, Giulio Pompilio
Over the past two decades cardiac cell therapy (CCT) has emerged as a promising new strategy to cure heart diseases at high unmet need. Thousands of patients have entered clinical trials for acute or chronic heart conditions testing different cell types, including autologous or allogeneic bone marrow (BM)-derived mononuclear or selected cells, BM- or adipose tissue-derived mesenchymal cells, or cardiac resident progenitors based on their potential ability to regenerate scarred or dysfunctional myocardium. Nowadays, the original enthusiasm surrounding the regenerative medicine field has been cushioned by a cumulative body of evidence indicating an inefficient or modest efficacy of CCT in improving cardiac function, along with the continued lack of indisputable proof for long-term prognostic benefit...
February 21, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28231509/a-single-injection-of-protein-loaded-coacervate-gel-significantly-improves-cardiac-function-post-infarction
#2
H K Awada, D W Long, Z Wang, M P Hwang, K Kim, Y Wang
After myocardial infarction (MI), the heart undergoes fibrotic pathological remodeling instead of repair and regeneration. With multiple pathologies developing after MI, treatment using several proteins is expected to address this range of pathologies more effectively than a single-agent therapy. A factorial design of experiments study guided us to combine three complementary factors in one injection: tissue inhibitor of metalloproteinases-3 (TIMP-3) was embedded in a fibrin gel for signaling in the initial phase of the treatment, while basic fibroblast growth factor (FGF-2) and stromal cell-derived factor 1-alpha (SDF-1α) were embedded in heparin-based coacervates for sustained release and distributed within the same fibrin gel to exert their effects over a longer period...
February 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28229425/optimal-environmental-stiffness-for-stem-cell-mediated-ischemic-myocardium-repair
#3
Honghai Liu, Christian Paul, Meifeng Xu
Cardiovascular diseases related to myocardial infarction (MI) contribute significantly to morbidity and mortality worldwide. The loss of cardiomyocytes during MI is a key factor in the impairment of cardiac-pump functions. Employing cell transplantation has shown great potential as a therapeutic approach in regenerating ischemic myocardium. Several studies have suggested that the therapeutic effects of stem cells vary based on the timing of cell administration. It has been clearly established that the myocardium post-infarction experiences a time-dependent stiffness change, and many studies have highlighted the importance of stiffness (elasticity) of microenvironment on modulating the fate and function of stem cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28229413/cardiac-progenitor-cell-extraction-from-human-auricles
#4
Paolo Di Nardo, Francesca Pagliari
For many years, myocardial tissue has been considered terminally differentiated and, thus, incapable of regenerating. Recent studies have shown, instead, that cardiomyocytes, at least in part, are slowly substituted by new cells originating by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient. The protocol here reported describes how from auricles a population of multipotent, cardiogenic cells can be isolated, cultured, and differentiated...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28229406/manipulating-the-proliferative-potential-of-cardiomyocytes-by-gene-transfer
#5
Giulia Prosdocimo, Mauro Giacca
In contrast to prenatal life, cardiomyocyte proliferation in mammals is rapidly blunted after birth; as a consequence, clinically significant cardiac regeneration does not occur in adulthood. Thus, the modulation of cardiomyocyte proliferation by gene transfer offers an invaluable opportunity to both understand the mechanisms regulating renewal of these cells in the fetus and identify novel strategies for myocardial repair.In this Chapter, we report an exhaustive protocol to isolate, culture, and manipulate the properties of neonatal ventricular rat cardiomyocytes by small RNA transfection or transduction with viral vectors based on the adeno-associated virus, which exhibit exquisite tropism for these cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28203749/ablation-of-periostin-inhibits-post-infarction-myocardial-regeneration-in-neonatal-mice-mediated-by-the-phosphatidylinositol-3-kinase-glycogen-synthase-kinase-3%C3%AE-cyclin-d1-signalling-pathway
#6
Zhenhuan Chen, Jiahe Xie, Huixin Hao, Hairuo Lin, Long Wang, Yingxue Zhang, Lin Chen, Shiping Cao, Xiaobo Huang, Wangjun Liao, Jianping Bin, Yulin Liao
No abstract text is available yet for this article.
February 14, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28194324/cell-therapies-in-cardiomyopathy-current-status-of-clinical-trials
#7
REVIEW
Ming Hao, Richard Wang, Wen Wang
Because the human heart has limited potential for regeneration, the loss of cardiomyocytes during cardiac myopathy and ischaemic injury can result in heart failure and death. Stem cell therapy has emerged as a promising strategy for the treatment of dead myocardium, directly or indirectly, and seems to offer functional benefits to patients. The ideal candidate donor cell for myocardial reconstitution is a stem-like cell that can be easily obtained, has a robust proliferation capacity and a low risk of tumour formation and immune rejection, differentiates into functionally normal cardiomyocytes, and is suitable for minimally invasive clinical transplantation...
2017: Analytical Cellular Pathology (Amsterdam)
https://www.readbyqxmd.com/read/28187777/gmp-conformant-on-site-manufacturing-of-a-cd133-stem-cell-product-for-cardiovascular-regeneration
#8
Anna Skorska, Paula Müller, Ralf Gaebel, Jana Große, Heiko Lemcke, Cornelia A Lux, Manuela Bastian, Frauke Hausburg, Nicole Zarniko, Sandra Bubritzki, Ulrike Ruch, Gudrun Tiedemann, Robert David, Gustav Steinhoff
BACKGROUND: CD133(+) stem cells represent a promising subpopulation for innovative cell-based therapies in cardiovascular regeneration. Several clinical trials have shown remarkable beneficial effects following their intramyocardial transplantation. Yet, the purification of CD133(+) stem cells is typically performed in centralized clean room facilities using semi-automatic manufacturing processes based on magnetic cell sorting (MACS®). However, this requires time-consuming and cost-intensive logistics...
February 10, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28186692/targeted-genome-engineering-to-control-vegf-expression-in-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-potential-implications-for-the-treatment-of-myocardial-infarction
#9
Hyun-Min Cho, Pyung-Hwan Kim, Hyun-Kyung Chang, Yi-Ming Shen, Kwaku Bonsra, Byung-Jae Kang, Soo-Young Yum, Joo-Hyun Kim, So-Yeong Lee, Min-Cheol Choi, Hyongbum Henry Kim, Goo Jang, Je-Yoel Cho
Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) exhibit potency for the regeneration of infarcted hearts. Vascular endothelial growth factor (VEGF) is capable of inducing angiogenesis and can boost stem cell-based therapeutic effects. However, high levels of VEGF can cause abnormal blood vessel growth and hemangiomas. Thus, a controllable system to induce therapeutic levels of VEGF is required for cell therapy. We generated an inducible VEGF-secreting stem cell (VEGF/hUCB-MSC) that controls the expression of VEGF and tested the therapeutic efficacy in rat myocardial infarction (MI) model to apply functional stem cells to MI...
January 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28185170/mechanisms-of-cardiomyocyte-proliferation-and-differentiation-in-development-and-regeneration
#10
REVIEW
Jessie Wettig Yester, Bernhard Kühn
PURPOSE OF REVIEW: Congenital heart disease is the most common birth defect and acquired heart disease is the leading cause of death in adults. Understanding the mechanisms that drive cardiomyocyte proliferation and differentiation has the potential to advance the understanding and potentially the treatment of different cardiac pathologies, ranging from myopathies and heart failure to myocardial infarction. This review focuses on studies aimed at elucidating signal transduction pathways and molecular mechanisms that promote proliferation, differentiation, and regeneration of differentiated heart muscle cells, cardiomyocytes...
February 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28170176/exosomes-derived-from-akt-modified-human-umbilical-cord-mesenchymal-stem-cells-improve-cardiac-regeneration-and-promote-angiogenesis-via-activating-platelet-derived-growth-factor-d
#11
Jie Ma, Yuanyuan Zhao, Li Sun, Xiaochun Sun, Xiaosu Zhao, Xiaoxian Sun, Hui Qian, Wenrong Xu, Wei Zhu
We have previously demonstrated the cardioprotective effects of exosomes derived from mesenchymal stem cells (MSCs). It is well known that the activation of Akt is involved in stem cell-induced cardioprotection. In the present study, we investigated whether exosomes released from Akt-overexpressing MSCs showed a beneficial effect on cardioprotection and angiogenesis. MSCs were collected from human umbilical cord (hucMSCs), and Akt was transfected into hucMSCs (Akt-hucMSCs) by using an adenovirus transfection system...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28155919/obtaining-spontaneously-beating-cardiomyocyte-like-cells-from-adipose-derived-stromal-vascular-fractions-cultured-on-enzyme-crosslinked-gelatin-hydrogels
#12
Gang Yang, Zhenghua Xiao, Xiaomei Ren, Haiyan Long, Kunlong Ma, Hong Qian, Yingqiang Guo
Heart failure often develops after acute myocardial infarction because the injured myocardial tissue fails to recover or regenerate. Stem cell transplantation using adult cell sources, such as adipose-derived stromal vascular fraction (SVF), draws extensive attention. In this study, SVF cells were isolated from rat adipose tissue and cultivated on enzyme-crosslinked gelatin hydrogels. Morphological features of cell development and spontaneous beating behavior from these cells were observed and recorded. Cardiac phenotypes were characterized via immunofluorescence staining, and the expression of cardiac-specific genes was measured via RT-PCR...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28138705/resveratrol-activates-endogenous-cardiac-stem-cells-and-improves-myocardial-regeneration-following-acute-myocardial-infarction
#13
Lin Ling, Shaohua Gu, Yan Cheng
Stem cell antigen-1-positive (Sca-1+) cardiac stem cells (CSCs) therapy for myocardial regeneration following acute myocardial infarction (AMI) is limited by insufficient cell viability and a high rate of apoptosis, due to the poor regional microenvironment. Resveratrol, which is a compound extracted from red wine, has been reported to protect myocardial tissue post‑AMI by increasing the expression of angiogenic and chemotactic factors. The present study aimed to investigate the effects of resveratrol on Sca‑1+ CSCs, and to optimize Sca‑1+ CSCs therapy for myocardial regeneration post‑AMI...
January 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28138518/decellularized-zebrafish-cardiac-extracellular-matrix-induces-mammalian-heart-regeneration
#14
William C W Chen, Zhouguang Wang, Maria Azzurra Missinato, Dae Woo Park, Daniel Ward Long, Heng-Jui Liu, Xuemei Zeng, Nathan A Yates, Kang Kim, Yadong Wang
Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracellular matrix (ECM) may contribute to this difference. Mammalian cardiac ECM may not be optimally inductive for cardiac regeneration because of the fibrotic, instead of regenerative, responses in injured adult mammalian hearts...
November 2016: Science Advances
https://www.readbyqxmd.com/read/28128477/cells-scaffolds-and-their-interactions-in-myocardial-tissue-regeneration
#15
Armita Mahdavi Gorabi, Seyed Hossein Ahmadi Tafti, Masoud Soleimani, Yunes Panahi, Amirhossein Sahebkar
Cardiac regenerative therapy includes several techniques to repair and replace damaged tissues and organs using cells, biomaterials, molecules or a combination of these factors. Generation of heart muscle is the most important challenge in this field, although it is well known that new advances in stem cell isolation and culture techniques in bioreactors and synthesis of bioactive materials contribute to the creation of cardiac tissue regeneration in vitro. Some investigations in stem cell biology show that stem cells are an important source for regeneration of heart muscle cells and blood vessels and can thus clinically contribute to the regeneration of damaged heart tissue...
January 27, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28116799/in-vitro-models-of-the-cardiac-microenvironment-to-study-myocyte-and-non-myocyte-crosstalk-bioinspired-approaches-beyond-the-polystyrene-dish
#16
Celinda M Kofron, Ulrike Mende
The heart is a complex pluricellular organ composed of cardiomyocytes and non-myocytes including fibroblasts, endothelial cells and immune cells. Myocytes are responsible for electrical conduction and contractile force generation, while the other cell types are responsible for matrix deposition, vascularization, and injury response. Myocytes and non-myocytes are known to communicate and exert mutual regulatory effects. In concert, they determine the structural, electrical and mechanical characteristics in the healthy and remodelled myocardium...
January 23, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28112546/characteristics-and-roles-of-exosomes-in-cardiovascular-disease
#17
Yuan Zhang, Yan-Wei Hu, Lei Zheng, Qian Wang
Exosomes are nano-sized biological membrane-enclosed vesicles that contain a cell-specific cargo of proteins, lipids, and nucleic acids that are released and taken up by most cell types, thereby inducing expression and functional changes via horizontal transfer of cargos between cells. Thus, exosomes present a largely unknown "cell-to-cell" communication system, which is now increasingly being investigated for diagnostic and therapeutic use in cardiovascular disease (CVD). The purpose of this review is to summarize recent findings on the properties and roles of exosomes in a variety of physiological and pathological settings related to CVD...
January 23, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28111317/transplantation-of-adipose-derived-stem-cells-combined-with-neuregulin-microparticles-promotes-efficient-cardiac-repair-in-a-rat-myocardial-infarction-model
#18
Paula Díaz-Herráez, Laura Saludas, Simón Pascual-Gil, Teresa Simón-Yarza, Gloria Abizanda, Felipe Prósper, Elisa Garbayo, María José Blanco-Prieto
Tissue engineering is a promising strategy to promote heart regeneration after a myocardial infarction (MI). In this study, we investigated the reparative potential of a system that combines adipose-derived stem cells (ADSCs) with microparticles (MPs) loaded with neuregulin (NRG), named ADSC-NRG-MPs, on a rat MI model. First, cells were attached to the surface of MPs encapsulating NRG and coated with a 1:1 mixture of collagen and poly-d-lysine. One week after in vivo administration, the system favored the shift of macrophage expression from a pro-inflammatory to a regenerative phenotype...
January 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28109258/effect-of-erythropoietin-in-patients-with-acute-myocardial-infarction-five-year-results-of-the-revival-3-trial
#19
Birgit Steppich, Philip Groha, Tareq Ibrahim, Heribert Schunkert, Karl-Ludwig Laugwitz, Martin Hadamitzky, Adnan Kastrati, Ilka Ott
BACKGROUND: Erythropoietin (EPO) has been suggested to promote cardiac repair after MI. However, the randomized, double-blind, placebo controlled REVIVAL-3 trial showed that short term high dose EPO in timely reperfused myocardium does not improve left ventricular ejection fraction after 6 months. Moreover, the study raised safety concerns due to a trend towards a higher incidence of adverse clinical events as well as a increase in neointima formation after treatment with EPO. The present study therefore aimed to assess the 5-year clinical outcomes...
January 21, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28086885/harnessing-the-early-post-injury-inflammatory-responses-for-cardiac-regeneration
#20
REVIEW
Bill Cheng, H C Chen, I W Chou, Tony W H Tang, Patrick C H Hsieh
Cardiac inflammation is considered by many as the main driving force in prolonging the pathological condition in the heart after myocardial infarction. Immediately after cardiac ischemic injury, neutrophils are the first innate immune cells recruited to the ischemic myocardium within the first 24 h. Once they have infiltrated the injured myocardium, neutrophils would then secret proteases that promote cardiac remodeling and chemokines that enhance the recruitment of monocytes from the spleen, in which the recruitment peaks at 72 h after myocardial infarction...
January 13, 2017: Journal of Biomedical Science
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