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.

scholarly journals Nanoengineering in Cardiac Regeneration: Looking Back and Going Forward

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1587
Author(s):  
Caterina Cristallini ◽  
Emanuela Vitale ◽  
Claudia Giachino ◽  
Raffaella Rastaldo
Keyword(s):  
Tissue Engineering ◽  
Experimental Study ◽  
Extracellular Matrix ◽  
Regenerative Medicine ◽  
Cardiac Tissue ◽  
Cardiac Regeneration ◽  
Cardiac Cells ◽  
Integration Process ◽  
Specific Interest ◽  
Looking Back

To deliver on the promise of cardiac regeneration, an integration process between an emerging field, nanomedicine, and a more consolidated one, tissue engineering, has begun. Our work aims at summarizing some of the most relevant prevailing cases of nanotechnological approaches applied to tissue engineering with a specific interest in cardiac regenerative medicine, as well as delineating some of the most compelling forthcoming orientations. Specifically, this review starts with a brief statement on the relevant clinical need, and then debates how nanotechnology can be combined with tissue engineering in the scope of mimicking a complex tissue like the myocardium and its natural extracellular matrix (ECM). The interaction of relevant stem, precursor, and differentiated cardiac cells with nanoengineered scaffolds is thoroughly presented. Another correspondingly relevant area of experimental study enclosing both nanotechnology and cardiac regeneration, e.g., nanoparticle applications in cardiac tissue engineering, is also discussed.

Abstract 359: The Production of Acellular Cardiac Extracellular Matrix from P3 Murine Heart

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Stefan M Kren ◽  
Daniel J Garry ◽  
Mary G Garry
Keyword(s):  
Extracellular Matrix ◽  
Cardiac Tissue ◽  
Fluorescent Protein ◽  
Cultured Cells ◽  
Culture Media ◽  
Heart Tissue ◽  
Cell Nuclei ◽  
Dapi Staining ◽  
Neonatal Heart ◽  
The Matrix

Introduction: Understanding the role of extracellular matrix (ECM) in the creation of the cellular microenvironment during tissue formation and regeneration could be vital in extending this capability to injured adult tissue. To date the only confirmed mammalian heart tissue regeneration/regrowth has been in neonatal murine heart, with the regenerative capacity ceasing after day P3. By focusing on ECM from P3 heart tissue we hope to elucidate its contribution to regenerative plasticity and transfer this capacity to injured adult myocardium. Hypothesis: Detergent decellularization protocols used in adult tissues can be modified to function on a neonatal scale, serving to remove the cellular components of the neonatal heart, leaving structurally intact ECM to serve as a scaffold for the generation of cardiac tissue equivalents. Materials and Methods: Murine P3 hearts were perfused with 1% SDS in water at 20mm Hg for 12 hrs. Following detergent decellularization, perfusion with water, 1% Triton X-100, PBS and culture media restored biocompatibility to the isolated ECM. P1 and P7 primary cardiomyocytes expressing the mCherry red fluorescent protein reporter under control of the alpha myosin promoter were isolated by enzymatic disassociation and cultured in the heart matrix in a perfusion based bioreactor. Results: The decellularized ECM demonstrated removal of 97% of native DNA when compared to control by pico-green dsDNA binding assay. Histologic analysis demonstrated an absence of cell nuclei by H & E and DAPI staining. The preservation of the matrix structure and the maintenance of matrix immunoreactivity (collagen IV) were also demonstrated histologically. Following infusion of P1 or P7 mCherry positive cells, contractile behavior of the recellularized heart constructs was observed, and markers of cardiac linage (alpha-actinin in mCherry positive cells) were present. Conclusions: Neonatal heart matrix can be effectively decellularized. With appropriate modification of perfusion parameters, pediatric ECM structure can be preserved. This isolated matrix can serve as a scaffold for growth and maintenance of immature and mature cardiomyocytes, supporting continued contractility of cultured cells.

scholarly journals Macrophage Polarization in Cardiac Tissue Repair Following Myocardial Infarction

2021 ◽  
Vol 22 (5) ◽  
pp. 2715
Author(s):  
Yevgeniy Kim ◽  
Sanzhar Nurakhayev ◽  
Ayan Nurkesh ◽  
Zharylkasyn Zharkinbekov ◽  
Arman Saparov
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Cardiac Tissue ◽  
Macrophage Polarization ◽  
Scar Tissue ◽  
M1 Macrophages ◽  
Mortality And Morbidity ◽  
Phenotypic Profile ◽  
Detrimental Impact ◽  
Alternatively Activated

Cardiovascular disease is the leading cause of mortality and morbidity around the globe, creating a substantial socio-economic burden as a result. Myocardial infarction is a significant contributor to the detrimental impact of cardiovascular disease. The death of cardiomyocytes following myocardial infarction causes an immune response which leads to further destruction of tissue, and subsequently, results in the formation of non-contractile scar tissue. Macrophages have been recognized as important regulators and participants of inflammation and fibrosis following myocardial infarction. Macrophages are generally classified into two distinct groups, namely, classically activated, or M1 macrophages, and alternatively activated, or M2 macrophages. The phenotypic profile of cardiac macrophages, however, is much more diverse and should not be reduced to these two subsets. In this review, we describe the phenotypes and functions of macrophages which are present in the healthy, as well as the infarcted heart, and analyze them with respect to M1 and M2 polarization states. Furthermore, we discuss therapeutic strategies which utilize macrophage polarization towards an anti-inflammatory or reparative phenotype for the treatment of myocardial infarction.

scholarly journals Engineering Extracellular Matrix Proteins to Enhance Cardiac Regeneration After Myocardial Infarction

2021 ◽  
Vol 8 ◽  
Author(s):  
Hamid Esmaeili ◽  
Chaoyang Li ◽  
Xing Fu ◽  
Jangwook P. Jung
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Cardiac Regeneration ◽  
Cardiac Cells ◽  
Matrix Proteins ◽  
Direct Integration ◽  
Compelling Evidence ◽  
Cardiomyocyte Proliferation ◽  
Myocardial Repair ◽  
Ecm Proteins

Engineering microenvironments for accelerated myocardial repair is a challenging goal. Cell therapy has evolved over a few decades to engraft therapeutic cells to replenish lost cardiomyocytes in the left ventricle. However, compelling evidence supports that tailoring specific signals to endogenous cells rather than the direct integration of therapeutic cells could be an attractive strategy for better clinical outcomes. Of many possible routes to instruct endogenous cells, we reviewed recent cases that extracellular matrix (ECM) proteins contribute to enhanced cardiomyocyte proliferation from neonates to adults. In addition, the presence of ECM proteins exerts biophysical regulation in tissue, leading to the control of microenvironments and adaptation for enhanced cardiomyocyte proliferation. Finally, we also summarized recent clinical trials exclusively using ECM proteins, further supporting the notion that engineering ECM proteins would be a critical strategy to enhance myocardial repair without taking any risks or complications of applying therapeutic cardiac cells.

scholarly journals Management and Outcomes of ST-segment Elevation Myocardial Infarction During Coronavirus 2019 Pandemic in a Center with 24/7 Primary Angioplasty Capability: Should We Change Our Practice During Outbreak?

2020 ◽  
Author(s):  
Mojtaba Salarifar ◽  
Mojgan Ghavami ◽  
Hamidreza Poorhosseini ◽  
Farzad Masoudkabir ◽  
Yaser Jenab ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Tissue ◽  
Tissue Injury ◽  
Coronary Intervention ◽  
Primary Angioplasty ◽  
Ct Imaging ◽  
Cardiac Events ◽  
Mortality And Morbidity ◽  
St Segment Elevation ◽  
The Difference

AbstractBackgroundST-Elevation Myocardial Infarction (STEMI) is associated with high mortality and morbidity. In order to minimize cardiac tissue injury, primary per-cutaneous coronary intervention (PPCI) as treatment of choice should be performed as soon as possible. Coronavirus Disease 2019 (COVID-19) as an ongoing major global concern affects the other parts of health care system. Applying preventive strategies during this outbreak is necessary. However, critical times in STEMI management and outcomes may be influenced by infection control protocols implementation. The aim of this study is to investigate the differences in time intervals related to STEMI care and 15-day major adverse cardiac events (MACE) during this outbreak compared with the same period in last year and to determine whether the STEMI protocol should be changed to thrombolytic therapy during COVID-19 outbreak or not.MethodsThe patients with STEMI who underwent PPCI in Tehran Heart Center were included. Chest Computed tomography (CT) imaging and real time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) were only performed for COVID-19 suspected patients. Seventy-seven patients from 29th February to 29th March 2020 were compared with 62 patients from 1st to 30th March 2019.ResultsCOVID-19 infection was confirmed by rRT-PCR in 5 cases. CT imaging in 4 out of 5 patients was in favor of COVID-19. The median of door-to-device time was reduced 13 minutes during this outbreak (p: 0.007). In-hospital mortality before and during outbreak was 3.22% and 5.19%, respectively (p: 0.57). Confirmed infection with COVID-19 was only reported in one of expired cases. The difference in 15-day MACE between two time periods was not statistically significant.Discussion/ConclusionGiven that 15-day outcome in acute STEMI patients is not affected by COVID-19 outbreak, we did not find it reasonable to change our protocol. However, further studies are needed to determine a standard protocol for emergency management.

scholarly journals Novel Applications of Mesenchymal Stem Cell-Derived Exosomes for Myocardial Infarction Therapeutics

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 707 ◽  
Author(s):  
Sho Joseph Ozaki Tan ◽  
Juliana Ferreria Floriano ◽  
Laura Nicastro ◽  
Costanza Emanueli ◽  
Francesco Catapano
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Tissue ◽  
Cardiac Cells ◽  
Therapeutic Effects ◽  
Multipotent Stem Cells ◽  
Mortality And Morbidity ◽  
Cell Therapies ◽  
State Of Research

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity globally, representing approximately a third of all deaths every year. The greater part of these cases is represented by myocardial infarction (MI), or heart attack as it is better known, which occurs when declining blood flow to the heart causes injury to cardiac tissue. Mesenchymal stem cells (MSCs) are multipotent stem cells that represent a promising vector for cell therapies that aim to treat MI due to their potent regenerative effects. However, it remains unclear the extent to which MSC-based therapies are able to induce regeneration in the heart and even less clear the degree to which clinical outcomes could be improved. Exosomes, which are small extracellular vesicles (EVs) known to have implications in intracellular communication, derived from MSCs (MSC-Exos), have recently emerged as a novel cell-free vector that is capable of conferring cardio-protection and regeneration in target cardiac cells. In this review, we assess the current state of research of MSC-Exos in the context of MI. In particular, we place emphasis on the mechanisms of action by which MSC-Exos accomplish their therapeutic effects, along with commentary on the current difficulties faced with exosome research and the ongoing clinical applications of stem-cell derived exosomes in different medical contexts.

scholarly journals Timing of Coronary Artery Bypass Grafting Surgery after Acute Myocardial Infarction

2020 ◽  
Author(s):  
Ahmed Fakhry ◽  
Yahia Balbaa ◽  
Waleed G Abo Senna ◽  
Hesham Z Saleh
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Mortality Rate ◽  
Artery Bypass ◽  
Total Mortality ◽  
Optimal Timing ◽  
University Hospitals ◽  
Mortality And Morbidity ◽  
Group 4 ◽  
Acute Mi

Background: Optimal timing for CABG surgery after myocardial infarction remains a matter of debate. The aim of our study was to analyze the effect of timing of CABG after acute myocardial infarction on operative mortality and morbidity. Methods: This prospective study included 60 patients who underwent isolated CABG within 30 days of acute myocardial infarction over 20 months (from the first of November 2014 till the end of June 2016) in Kasr Al-Ainy University Hospitals. Patients were divided into two groups; the early group (0 – 3 days) included 14 patients (23.3%) and the late group (4 – 30 days) included 46 patients (76.7%). The primary outcome was all-cause hospital mortality. Results: Our study included 43 males (71.7%) and 17 females (28.3%). The mean age was 58.4 ± 7.3 years. The total mortality rate was 8.3%. Patients undergoing early CABG experienced a higher mortality rate than those undergoing late CABG (21.4% vs 4.3%, P = 0.043). Also, early CABG was associated with more postoperative complications. Cardiogenic shock and early CABG were independent risk factors of mortality. Conclusion: CABG in the first 3 days after acute myocardial infarction was associated with high mortality and morbidity in comparison with late CABG. This suggests that CABG may best be deferred for more than 3 days after acute MI in non-urgent cases.

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.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

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