Abstract 221: Tannic Acid Coated Nanoparticles for Cardiac Regeneration

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Giulia Torrieri ◽  
Mónica P Ferreira ◽  
Mohammad-Ali Shahbazi ◽  
Virpi Talman ◽  
Cláudia Carvalho ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Tannic Acid ◽  
Cardiac Tissue ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Direct Reprogramming ◽  
Rat Cardiomyocytes ◽  
Coated Nanoparticles ◽  
Primary Fibroblasts ◽  
Acid Coating

The advance of nanomedicines has recently offered novel approaches to tackle cardiovascular diseases and, in particular, myocardial infarction (MI). However, the constant pumping of the heart and the still poor knowledge of targetable moieties, prevented the application of nanomedicines in the cardiovascular field to rise. Tannic acid, a polyphenol derived from plants, has showed affinity for components of the extracellular matrix, in particular elastin, allowing the retention of protein aggregates in the cardiac tissue. Here, we explored the heart targeting abilities of tannic acid by using it to coat spermine modified-acetalated dextran (AcDXSp) nanoparticles (NPs). Briefly, particles were prepared by single emulsion technique and then coated with tannic acid by complexation of the polyphenol with Fe 3+ ions, resulting in the formation of a capsule around the AcDXSp NPs. The nanoparticles were loaded with two small hydrophobic compounds, CHIR99021 and SB431542, which were both proven to increase the efficiency of direct reprogramming of fibroblasts into cardiomyocytes. The biocompatibility of the nanosystem and cellular uptake were performed on both primary rat cardiomyocytes and fibroblasts. The nanoparticles were taken-up by both the cell types and were safe towards primary cardiomyocytes, while the tannic acid coating showed anti-fibrotic effects on primary fibroblasts. Anti-fibrotic effect was further confirmed by RT-qPCR and the effect of the loaded compounds was assessed by β-catenin and Smad3 immunostainings, which demonstrated the ability of the system to induce direct reprogramming of fibroblasts into cardiomyocytes. In particular, the system stabilized β-catenin and prevented the translocation of Smad3 to the nucleus of myo(fibroblasts). In conclusion this nanosystems exhibited potential to tackle the negative fibrosis process occurring after myocardial infarction by both contrasting it, due to the anti-fibrotic effects showed by the tannic acid coating and by potentially regenerating the cardiac tissue, due to the efficient direct reprogramming of fibroblasts into cardiomyocytes exerted by the loaded drugs.

scholarly journals Changes in IGFs in cardiac tissue following myocardial infarction

1999 ◽  
Vol 163 (3) ◽  
pp. 433-445 ◽  
Author(s):  
KG Matthews ◽  
GP Devlin ◽  
JV Conaglen ◽  
SP Stuart ◽  
W Mervyn Aitken ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Binding Proteins ◽  
Cardiac Tissue ◽  
Apoptotic Cell ◽  
Specific Binding ◽  
Cell Types ◽  
Necrotic Tissue ◽  
Igf I ◽  
The Relationship

We have studied changes in the IGF axis in an ovine model of myocardial infarction (MI), in order to determine the relationship between time-based changes in post-infarct myocardium and IGF levels. IGF localization was studied by immunocytochemistry, production by in situ hybridization, and specific binding by radioligand studies. In surviving tissue, IGF-I peptide localized to cardiomyocytes, with strongest immunostaining at 1 and 2 days post-infarct in the immediate border area adjoining the infarct, where IGF-I mRNA also increased, reaching a maximum at 2 days. Binding of radiolabelled IGF-I in surviving tissue was initially lower than that seen in cardiomyocytes in control myocardium, subsequently increasing to become significantly greater by 6 days post-infarct. In necrotic tissue, IGF-I peptide was still detectable in cardiomyocytes at 0.5 days post-infarct, but had cleared from this area by 1 day, becoming detectable again at 6 days post-infarct in macrophages and fibroblasts infiltrating the repair zone. IGF-I mRNA was not detected in necrotic tissue until 6 days, when probe hybridized to macrophages and fibroblasts. Within the necrotic zone, high levels of radiolabelled IGF-I binding to a combination of receptors and binding proteins were observed in cardiomyocytes in islands of viable tissue located close to the border. Weak immunostaining for IGF-II was observed in cardiomyocytes of the surviving tissue. IGF-II mRNA was not detected in either surviving or necrotic areas. Binding of radiolabelled IGF-II was predominantly to macrophages in both surviving and infarct areas, although as with IGF-I, high levels of binding of radiolabelled IGF-II to a combination of receptors and binding proteins were observed in islands of viable tissue close to the border within the necrotic area. We conclude that, following MI, surviving cardiomyocytes at the infarct border show marked changes in IGF-I localization, production, and specific binding, indicating that the IGF axis is directly involved in post-infarct events, possibly in the maintenance of cardiac function by the induction of hypertrophy and in cell survival by decreasing apoptotic cell death, which has been demonstrated in other cell types.

scholarly journals Epicardial therapy with atrial appendage micrografts salvages myocardium after infarction

2019 ◽  
Author(s):  
Xie Yanbo ◽  
Milla Lampinen ◽  
Juuso Takala ◽  
Vilbert Sikorski ◽  
Rabah Soliymani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Cardiac Tissue ◽  
Artery Bypass ◽  
Cardiac Regeneration ◽  
Atrial Appendage ◽  
Mortality And Morbidity ◽  
The Matrix ◽  
Clinical Benefits ◽  
Matrix Patch

AbstractIschemic heart disease remains the leading cause of mortality and morbidity worldwide despite improved possibilities in medical care. Alongside interventional therapies, such as coronary artery bypass grafting, adjuvant tissue-engineered and cell-based treatments can provide regenerative improvement. Unfortunately, most of these advanced approaches require multiple lengthy and costly preparation stages without delivering significant clinical benefits.We evaluated the effect of epicardially delivered minute pieces of atrial appendage tissue material, defined as atrial appendage micrografts (AAMs), in mouse myocardial infarction model. An extracellular matrix patch was used to cover and fix the AAMs onto the surface of the infarcted heart. The matrix-covered AAMs salvaged the heart from infarction-induced loss of functional myocardium and attenuated scarring. Site-selective proteomics of injured ischemic and uninjured distal myocardium from AAM-treated and untreated tissue sections revealed an increased expression of several cardiac regeneration-associated proteins (i.e. periostin, transglutaminases and glutathione peroxidases) as well as activation of pathways responsible for angio- and cardiogenesis in relation to AAMs therapy.Epicardial delivery of AAMs encased in an extracellular matrix patch scaffold salvages functional cardiac tissue from ischemic injury and restricts fibrosis after myocardial infarction. Our results support the use of AAMs as tissue-based therapy adjuvants for salvaging the ischemic myocardium.

Mini Review: Recent Advances in the Cell-Based Therapies for Cardiac Regeneration

2020 ◽  
Vol 15 (8) ◽  
pp. 649-660 ◽  
Author(s):  
Lan Luo ◽  
Tao-Sheng Li
Keyword(s):  
Cardiac Fibroblasts ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Cardiac Stem Cells ◽  
Direct Reprogramming ◽  
Promising Candidate ◽  
Surgical Interventions ◽  
Skeletal Myoblasts ◽  
Novel Approach ◽  
Induced Pluripotent

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality globally, and traditional pharmaceutical and surgical interventions delay the progression of CVDs. Recently, stem cell therapy has emerged as a promising candidate for treating and preventing heart failure. Increasing efforts have been devoted towards the exploration and identification of potential cell types to repair the injured heart, such as skeletal myoblasts, embryonic, induced pluripotent, bone marrowderived, mesenchymal, and resident cardiac stem cells. In addition, direct reprogramming of cardiac fibroblasts into cardiomyocytes represents a novel approach to cardiac regeneration. Herein, we summarize the recent progress in the use of various cell types for cardiac regeneration and discuss major challenges and future perspectives of cell-based therapies for CVDs.

scholarly journals New Strategies to Enhance Myocardial Regeneration: Expectations and Challenges from Preclinical Evidence

2020 ◽  
Vol 15 (8) ◽  
pp. 696-710 ◽  
Author(s):  
Erica Rurali ◽  
Maria Cristina Vinci ◽  
Beatrice Bassetti ◽  
Veronica Barbagallo ◽  
Giulio Pompilio ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Myocardial Remodeling ◽  
Physiological Conditions ◽  
Cell Efficiency ◽  
Different Types ◽  
Preclinical Trials ◽  
New Strategies

Nowadays, cardiac regeneration is an emerging topic in the cardiovascular field because of the compelling need for effective therapies for repairing or replacing cardiac tissue damaged by pathological or physiological conditions. Indeed, irreversible myocardial remodeling which follows acute myocardial infarction represents a serious burden of this century. In this context, a great improvement in pharmacological and interventional techniques is accompanied by a big challenge of cardiac regenerative medicine. In the last 20 years, several clinical trials tried to investigate the role of different types of stem cells in promoting cardiac repair. However, the promising results obtained in the preclinical trials have not yet been reproduced in patients. Thus, the development of novel strategies to improve stem cell efficiency became imperative. Here, an overview of the more recent cell types proposed for cardiac regeneration is presented, together with the most interesting approaches to enhance cell regenerative potential as well as cell-free approaches.

scholarly journals Polymeric Biomaterials for the Treatment of Cardiac Post-Infarction Injuries

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1038
Author(s):  
Sonia Trombino ◽  
Federica Curcio ◽  
Roberta Cassano ◽  
Manuela Curcio ◽  
Giuseppe Cirillo ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cardiac Tissue ◽  
Polymeric Nanoparticles ◽  
Three Dimensional ◽  
Cardiac Regeneration ◽  
Biological Properties ◽  
Positive Influence ◽  
Regenerative Process ◽  
Current Status ◽  
Polymeric Biomaterials

Cardiac regeneration aims to reconstruct the heart contractile mass, preventing the organ from a progressive functional deterioration, by delivering pro-regenerative cells, drugs, or growth factors to the site of injury. In recent years, scientific research focused the attention on tissue engineering for the regeneration of cardiac infarct tissue, and biomaterials able to anatomically and physiologically adapt to the heart muscle have been proposed as valuable tools for this purpose, providing the cells with the stimuli necessary to initiate a complete regenerative process. An ideal biomaterial for cardiac tissue regeneration should have a positive influence on the biomechanical, biochemical, and biological properties of tissues and cells; perfectly reflect the morphology and functionality of the native myocardium; and be mechanically stable, with a suitable thickness. Among others, engineered hydrogels, three-dimensional polymeric systems made from synthetic and natural biomaterials, have attracted much interest for cardiac post-infarction therapy. In addition, biocompatible nanosystems, and polymeric nanoparticles in particular, have been explored in preclinical studies as drug delivery and tissue engineering platforms for the treatment of cardiovascular diseases. This review focused on the most employed natural and synthetic biomaterials in cardiac regeneration, paying particular attention to the contribution of Italian research groups in this field, the fabrication techniques, and the current status of the clinical trials.

Flow Cytometric Evaluation of the Ongoing Angiogenic Response in Rat Cardiac Tissue Following Myocardial Infarction

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Cecilie Hoeeg ◽  
Lars Ringgaard ◽  
Esben Christensen ◽  
Bjarke Follin ◽  
Simon Bentsen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Tissue ◽  
Angiogenic Response ◽  
Flow Cytometric ◽  
Flow Cytometric Evaluation

scholarly journals Synthesis of Silica Nanoparticles with Physical Encapsulation of Near-Infrared Fluorescent Dyes and Their Tannic Acid Coating

ACS Omega ◽  
2021 ◽  
Author(s):  
Yoshio Nakahara ◽  
Yukiho Nakajima ◽  
Soichiro Okada ◽  
Jun Miyazaki ◽  
Setsuko Yajima
Keyword(s):  
Silica Nanoparticles ◽  
Tannic Acid ◽  
Near Infrared ◽  
Fluorescent Dyes ◽  
Acid Coating

Involvement of monocytes/macrophages as key factors in the development and progression of cardiovascular diseases

2014 ◽  
Vol 458 (2) ◽  
pp. 187-193 ◽  
Author(s):  
María Fernández-Velasco ◽  
Silvia González-Ramos ◽  
Lisardo Boscá
Keyword(s):  
Myocardial Infarction ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Initial Period ◽  
Cardiac Injury ◽  
Key Factors ◽  
Cardiac Damage ◽  
Inflammatory Profile

Emerging evidence points to the involvement of specialized cells of the immune system as key drivers in the pathophysiology of cardiovascular diseases. Monocytes are an essential cell component of the innate immune system that rapidly mobilize from the bone marrow to wounded tissues where they differentiate into macrophages or dendritic cells and trigger an immune response. In the healthy heart a limited, but near-constant, number of resident macrophages have been detected; however, this number significantly increases during cardiac damage. Shortly after initial cardiac injury, e.g. myocardial infarction, a large number of macrophages harbouring a pro-inflammatory profile (M1) are rapidly recruited to the cardiac tissue, where they contribute to cardiac remodelling. After this initial period, resolution takes place in the wound, and the infiltrated macrophages display a predominant deactivation/pro-resolution profile (M2), promoting cardiac repair by mediating pro-fibrotic responses. In the present review we focus on the role of the immune cells, particularly in the monocyte/macrophage population, in the progression of the major cardiac pathologies myocardial infarction and atherosclerosis.

Abstract 17093: Human Neonatal Cardiac Mesenchymal Stem Cells Demonstrates Superior Cardiac Regenerative Abilities Compared to Other Stem Cells

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Muthukumar Gunasekaran ◽  
Rachana Mishra ◽  
Progyaparamita Saha ◽  
Xuebin Fu ◽  
Mohamed Abdullah ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Inflammatory Cytokines ◽  
Cell Types ◽  
Wild Type ◽  
Cell Type ◽  
Anti Inflammatory ◽  
Stem Cell Type

Stem cells transplantation is being explored as an effective therapy for heart diseases. However, majority of stem cell therapies for adult patients with myocardial infarction (MI) had mixed and inconsistent results implying chronological age may influence the effectiveness of regenerative therapies. Therefore, herein, we performed a head-to-head comparison between different, well-studied stem cell types to identify the superior regenerative cell type using rodent MI model.After our standard characterization for each stem cell type (FACS for cell surface markers), 1 million neonatal Cardiac Mesenchymal Stem cells (nMSCs), adult MSCs (aMSCs), adult derived cardiosphere derived cells (aCDCs), umbilical cord derived cells (UCBCs), Bone Marrow derived Mesenchymal Stem cells (BM-MSCs), or cell-free Iscove Modified Dulbecco Medium (IMDM as placebo control) were injected into athymic rat myocardial infarct model. Although all the tested groups significantly improved ejection fraction, nMSCs outperformed other stem cells in cardiac functional recovery. Additionally, nMSCs also showed significant increased cardiac functional recovery compared to aMSCs in wild type rat MI model. Mason trichrome staining with heart sections revealed that decreased fibrosis was evident on nMSCs injection compared to aMSCs in both athymic and wild type rat MI model. Myocardial sections from rats received nMSCs showed significantly reduced M1 macrophages (inflammatory) and increased M2 macrophages (anti-inflammatory) compared with sections from rats having received aMSCs and IMDM control. Pro and anti-inflammatory cytokines analyzed on sera collected on day 2 and 7 revealed that anti-inflammatory cytokine (IL10) was significantly increased and inflammatory cytokines (IL4 and IL12) reduced in nMSCs compared to aMSCs transplanted MI rat model.In conclusion, nMSCs demonstrated superior functional abilities, reduced fibrosis, inflammatory cells and cytokines compared to all the other cell types and with aMSCs demonstrating that nMSCs is an ideal stem cell type for therapeutic application in myocardial infarction.

Cannabinoids and myocardial ischemia: Novel insights, updated mechanisms, and implications for myocardial infarction

2021 ◽  
Vol 28 ◽  
Author(s):  
Karim Seif El-Dahan ◽  
Dima Machtoub ◽  
Gaelle Massoud ◽  
Suzanne A. Nasser ◽  
Bassam Hamam ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Illicit Drugs ◽  
Supply And Demand ◽  
Health Benefits ◽  
Cell Types ◽  
Cellular Mechanisms ◽  
Potential Health ◽  
Organ Systems ◽  
Increased Risk

: Cannabis is the most widely trafficked and abused illicit drug due to its calming psychoactive properties. It has been increasingly recognized as having potential health benefits and relatively less adverse health effects as compared to other illicit drugs; however, growing evidence clearly indicates that cannabis is associated with considerable adverse cardiovascular events. Recent studies have linked cannabis use to myocardial infarction (MI); yet, very little is known about the underlying mechanisms. A MI is a cardiovascular disease characterized by a mismatch in the oxygen supply and demand of the heart, resulting in ischemia and subsequent necrosis of the myocardium. Since cannabis is increasingly being considered a risk factor for MI, there is a growing need for better appreciating its potential health benefits and consequences. Here, we discuss the cellular mechanisms of cannabis that lead to an increased risk of MI. We provide a thorough and critical analysis of cannabinoids’ actions, which include modulation of adipocyte biology, regional fat distribution, and atherosclerosis, as well as precipitation of hemodynamic stressors relevant in the setting of a MI. By critically dissecting the modulation of signaling pathways in multiple cell types, this paper highlights the mechanisms through which cannabis may trigger life-threatening cardiovascular events. This then provides a framework for future pharmacological studies which can identify targets or develop drugs that modulate cannabis’ effects on the cardiovascular system as well as other organ systems. Cannabis’ impact on the autonomic outflow, vascular smooth muscle cells, myocardium, cortisol levels and other hemodynamic changes are also mechanistically reviewed.

Sign in / Sign up

Export Citation Format

Share Document