scholarly journals Biomaterials Loaded with Growth Factors/Cytokines and Stem Cells for Cardiac Tissue Regeneration

2020 ◽  
Vol 21 (17) ◽  
pp. 5952 ◽  
Author(s):  
Saltanat Smagul ◽  
Yevgeniy Kim ◽  
Aiganym Smagulova ◽  
Kamila Raziyeva ◽  
Ayan Nurkesh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Tissue Damage ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Left Ventricle Remodeling ◽  
And Migration

Myocardial infarction causes cardiac tissue damage and the release of damage-associated molecular patterns leads to activation of the immune system, production of inflammatory mediators, and migration of various cells to the site of infarction. This complex response further aggravates tissue damage by generating oxidative stress, but it eventually heals the infarction site with the formation of fibrotic tissue and left ventricle remodeling. However, the limited self-renewal capability of cardiomyocytes cannot support sufficient cardiac tissue regeneration after extensive myocardial injury, thus, leading to an irreversible decline in heart function. Approaches to improve cardiac tissue regeneration include transplantation of stem cells and delivery of inflammation modulatory and wound healing factors. Nevertheless, the harsh environment at the site of infarction, which consists of, but is not limited to, oxidative stress, hypoxia, and deficiency of nutrients, is detrimental to stem cell survival and the bioactivity of the delivered factors. The use of biomaterials represents a unique and innovative approach for protecting the loaded factors from degradation, decreasing side effects by reducing the used dosage, and increasing the retention and survival rate of the loaded cells. Biomaterials with loaded stem cells and immunomodulating and tissue-regenerating factors can be used to ameliorate inflammation, improve angiogenesis, reduce fibrosis, and generate functional cardiac tissue. In this review, we discuss recent findings in the utilization of biomaterials to enhance cytokine/growth factor and stem cell therapy for cardiac tissue regeneration in small animals with myocardial infarction.

scholarly journals Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

2020 ◽  
Vol 21 (19) ◽  
pp. 7301 ◽  
Author(s):  
Kamila Raziyeva ◽  
Aiganym Smagulova ◽  
Yevgeniy Kim ◽  
Saltanat Smagul ◽  
Ayan Nurkesh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Heart Function ◽  
Cellular Reprogramming ◽  
Genetic Manipulations ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Ischemic heart disease and myocardial infarction remain leading causes of mortality worldwide. Existing myocardial infarction treatments are incapable of fully repairing and regenerating the infarcted myocardium. Stem cell transplantation therapy has demonstrated promising results in improving heart function following myocardial infarction. However, poor cell survival and low engraftment at the harsh and hostile environment at the site of infarction limit the regeneration potential of stem cells. Preconditioning with various physical and chemical factors, as well as genetic modification and cellular reprogramming, are strategies that could potentially optimize stem cell transplantation therapy for clinical application. In this review, we discuss the most up-to-date findings related to utilizing preconditioned stem cells for myocardial infarction treatment, focusing mainly on preconditioning with hypoxia, growth factors, drugs, and biological agents. Furthermore, genetic manipulations on stem cells, such as the overexpression of specific proteins, regulation of microRNAs, and cellular reprogramming to improve their efficiency in myocardial infarction treatment, are discussed as well.

scholarly journals Immunomodulatory Functions of Mesenchymal Stem Cells in Tissue Engineering

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Haojiang Li ◽  
Shi Shen ◽  
Haitao Fu ◽  
Zhenyong Wang ◽  
Xu Li ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Tissue Damage ◽  
Material Selection ◽  
Immune Microenvironment ◽  
Chronic Injury ◽  
Research Fields

The inflammatory response to chronic injury affects tissue regeneration and has become an important factor influencing the prognosis of patients. In previous stem cell treatments, it was revealed that stem cells not only have the ability for direct differentiation or regeneration in chronic tissue damage but also have a regulatory effect on the immune microenvironment. Stem cells can regulate the immune microenvironment during tissue repair and provide a good “soil” for tissue regeneration. In the current study, the regulation of immune cells by mesenchymal stem cells (MSCs) in the local tissue microenvironment and the tissue damage repair mechanisms are revealed. The application of the concepts of “seed” and “soil” has opened up new research avenues for regenerative medicine. Tissue engineering (TE) technology has been used in multiple tissues and organs using its biomimetic and cellular cell abilities, and scaffolds are now seen as an important part of building seed cell microenvironments. The effect of tissue engineering techniques on stem cell immune regulation is related to the shape and structure of the scaffold, the preinflammatory microenvironment constructed by the implanted scaffold, and the material selection of the scaffold. In the application of scaffold, stem cell technology has important applications in cartilage, bone, heart, and liver and other research fields. In this review, we separately explore the mechanism of MSCs in different tissue and organs through immunoregulation for tissue regeneration and MSC combined with 3D scaffolds to promote MSC immunoregulation to repair damaged tissues.

scholarly journals PEMANFAATAN SEL PUNCA PADA INFARK MIOKARD

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Loretta C. Wangko ◽  
J. H. Awaloei ◽  
Janry A. Pangemanan
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Tissue Repair ◽  
Heart Function ◽  
Improve Heart Function ◽  
Β Blockers ◽  
Causes Of Deaths ◽  
Myocardial Thickness

Abstract: World-wide, myocardial infarction and heart failure are still the leading causes of deaths and use up a great deal of money. In myocardial infarction there frequently incur cardiomyocyte injuries. Naturally, resident cardiomyocytes will undergo proliferation and contribute to the increasing and repairing of myocardium post infarction. Unfortunately, this capacity of regeneration is very limited. Moreover, injured cardiomyocytes are replaced by scar tissues. Pharmacotherapy with ACE-Inhibitors and β blockers can give some clinical improvement, but can not inhibit the loss of cardiomyocytes. Nowadays, stem cell therapy has proclaimed some promising benefits. Among all the introduced stem cells, mesenchymal stem cells are the most popular since they have the capability to differentiate and then to develop into cardiomyocytes, maintain the myocardial thickness, reduce heart remodeling of the non infarct myocardium, improve heart function, and can be used from allogenic donors. Besides that, these cells are easier to obtain and isolate, are genetically stable, have the capacity for angiogenesis, homing to the injured areas or inflammation, and supplying growth factors and cytokines for tissue repair. Key words: stem cell, cardiomyocyte, transplantation, donor.     Abstrak: Infark miokard dan gagal jantung masih merupakan penyebab kematian utama di dunia dan menyerap biaya pengobatan yang tinggi. Pada infark miokard sering terjadi cedera kardiomiosit. Secara alamiah kardiomiosit residen akan mengalami proliferasi dan mengambil bagian dalam meningkatkan dan memulihkan miokard pasca infark. Kapasitas regenerasi ini sangat terbatas. Selain itu kardiomiosit yang cedera akan digantikan oleh jaringan ikat. Farmakoterapi dengan penghambat ACE dan β bloker dapat memberikan perbaikan klinis, tetapi tidak dapat menghambat kehilangan kardiomiosit. Dewasa ini terapi sel punca telah mengumandangkan manfaat yang menjanjikan. Dari berbagai sel punca yang dikemukakan, sel punca mesensimal yang paling diminati oleh karena kemampuannya berdiferensiasi dan berkembang menjadi kardiomiosit, mempertahankan ketebalan miokard, menurunkan remodeling jantung pada bagian yang tidak infark, memperbaiki fungsi jantung. dan dapat diambil dari donor alogenik. Disamping itu, sel-sel ini lebih mudah diperoleh dan diisolasi, stabil secara genetik, berkapasitas angiogenesis, homing ke tempat cedera atau inflamasi, dan memasok growth factors dan sitokin untuk perbaikan jaringan. Kata kunci: sel punca, kardiomiosit, transplantasi, donor.

scholarly journals Effects of Lipids and Lipoproteins on Mesenchymal Stem Cells Used in Cardiac Tissue Regeneration

2020 ◽  
Vol 21 (13) ◽  
pp. 4770 ◽  
Author(s):  
Yi-Hsiung Lin ◽  
Lin Kang ◽  
Wen-Han Feng ◽  
Tsung-Lin Cheng ◽  
Wei-Chung Tsai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Tissue Regeneration ◽  
Blood Lipids ◽  
Cardiac Tissue ◽  
Lipid Lowering ◽  
Lipids And Lipoproteins ◽  
Msc Differentiation

Mesenchymal stem cells (MSCs) have two characteristics of interest for this paper: the ability to self-renew, and the potential for multiple-lineage differentiation into various cells. MSCs have been used in cardiac tissue regeneration for over a decade. Adult cardiac tissue regeneration ability is quite low; it cannot repair itself after injury, as the heart cells are replaced by fibroblasts and lose function. It is therefore important to search for a feasible way to repair and restore heart function through stem cell therapy. Stem cells can differentiate and provide a source of progenitor cells for cardiomyocytes, endothelial cells, and supporting cells. Studies have shown that the concentrations of blood lipids and lipoproteins affect cardiovascular diseases, such as atherosclerosis, hypertension, and obesity. Furthermore, the MSC lipid profiles, such as the triglyceride and cholesterol content, have been revealed by lipidomics, as well as their correlation with MSC differentiation. Abnormal blood lipids can cause serious damage to internal organs, especially heart tissue. In the past decade, the accumulated literature has indicated that lipids/lipoproteins affect stem cell behavior and biological functions, including their multiple lineage capability, and in turn affect the outcome of regenerative medicine. This review will focus on the effect of lipids/lipoproteins on MSC cardiac regenerative medicine, as well as the effect of lipid-lowering drugs in promoting cardiomyogenesis-associated MSC differentiation.

scholarly journals Combinatorial treatment of acute myocardial infarction using stem cells and their derived exosomes resulted in improved heart performance

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Peisen Huang ◽  
Li Wang ◽  
Qing Li ◽  
Jun Xu ◽  
Junyan Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Function ◽  
Inflammatory Responses ◽  
Heart Function ◽  
Border Zone ◽  
Inflammatory Factor ◽  
Intramyocardial Injection

Abstract Background Bone marrow mesenchymal stem cells (MSCs) are among the most common cell types to be used and studied for cardiac regeneration. Low survival rate and difficult retention of delivered MSCs in infarcted heart remain as major challenges in the field. Co-delivery of stem cell-derived exosomes (Exo) is expected to improve the recruitment and survival of transplanted MSCs. Methods Exo was isolated from MSCs and delivered to an acute myocardial infarction (AMI) rat heart through intramyocardial injection with or without intravenous infusion of atrovastatin-pretreated MSCs on day 1, day 3, or day 7 after infarction. Echocardiography was performed to evaluate cardiac function. Histological analysis and ELISA test were performed to assess angiogenesis, SDF-1, and inflammatory factor expression in the infarct border zone. The anti-apoptosis effect of Exo on MSCs was evaluated using flow cytometry and Hoechst 33342 staining assay. Results We found that intramyocardial delivery of Exo followed by MSC transplantation (in brief, Exo+MSC treatment) into MI hearts further improved cardiac function, reduced infarct size, and increased neovascularization when compared to controls treated with Exo or MSCs alone. Of note, comparing the three co-transplanting groups, intramyocardially injecting Exo 30 min after AMI combined with MSCs transplantation at day 3 after AMI achieved the highest improvement in heart function. The observed enhanced heart function is likely due to an improved microenvironment via Exo injection, which is exemplified as reduced inflammatory responses and better MSC recruitment and retention. Furthermore, we demonstrated that pre-transplantation injection of Exo enhanced survival of MSCs and reduced their apoptosis both in vitro and in vivo. Conclusions Combinatorial delivery of exosomes and stem cells in a sequential manner effectively reduces scar size and restores heart function after AMI. This approach may represent as an alternative promising strategy for stem cell-based heart repair and therapy.

Bone marrow mesenchymal stem cells overexpressing GATA-4 improve cardiac function following myocardial infarction

Perfusion ◽  
2019 ◽  
Vol 34 (8) ◽  
pp. 696-704 ◽  
Author(s):  
Ji-Gang He ◽  
Hong-Rong Li ◽  
Bei-Bei Li ◽  
Qiao-Li Xie ◽  
Dan Yan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cardiac Function ◽  
Cardiac Tissue ◽  
Cell Group ◽  
Marrow Mesenchymal Stem Cells

Introduction: The present study aimed to examine whether GATA-4 overexpressing bone marrow mesenchymal stem cells can improve cardiac function in a murine myocardial infarction model compared with bone marrow mesenchymal stem cells alone. Methods: A lentiviral-based transgenic system was used to generate bone mesenchymal stem cells which stably expressed GATA-4 (GATA-4-bone marrow mesenchymal stem cells). Apoptosis and the myogenic phenotype of the bone marrow mesenchymal stem cells were measured using Western blot and immunofluorescence assays co-cultured with cardiomyocytes. Cardiac function, bone marrow mesenchymal stem cell homing, cardiac cell apoptosis, and vessel number following transplantation were assessed, as well as the expression of c-Kit. Results: In GATA-4-bone marrow mesenchymal stem cells-cardiomyocyte co-cultures, expression of myocardial-specific antigens, cTnT, connexin-43, desmin, and α-actin was increased compared with bone marrow mesenchymal stem cells alone. Caspase 8 and cytochrome C expression was lower, and the apoptotic rate was significantly lower in GATA-4 bone marrow mesenchymal stem cells. Cardiac function following myocardial infarction was also increased in the GATA-4 bone marrow mesenchymal stem cell group as demonstrated by enhanced ejection fraction and left ventricular fractional shortening. Analysis of the cardiac tissue revealed that the GATA-4 bone marrow mesenchymal stem cell group had a greater number of DiR-positive cells suggestive of increased homing and/or survival. Transplantation with GATA-4-bone marrow mesenchymal stem cells significantly increased the number of blood vessels, decreased the proportion of apoptotic cells, and increased the mean number of cardiac c-kit-positive cells. Conclusion: GATA-4 overexpression in bone marrow mesenchymal stem cells exerts anti-apoptotic effects by targeting cytochrome C and Fas pathways, promotes the aggregation of bone marrow mesenchymal stem cells in cardiac tissue, facilitates angiogenesis, and effectively mobilizes c-kit-positive cells following myocardial infarction, leading to the improvement of cardiac function after MI.

Abstract 197: Plasminogen Is Required for Hematopoietic Stem Cell-Mediated Cardiac Repair After Myocardial Infarction

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Yanqing Gong ◽  
Ying Li ◽  
Jane Hoover-Plow
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Heart Function ◽  
Critical Role ◽  
The United States ◽  
Cardiac Repair ◽  
Internal Diameter ◽  
Hematopoietic Stem

Myocardial infarction (MI) is the primary cause of death throughout the United States. Granulocyte colony-stimulating factor (G-CSF) is used to mobilize hematopoietic progenitor and stem cells (HPSC) to improve cardiac recovery after MI. However, poor-mobilization to G-CSF is observed in 25% of patients and 10-20% of healthy donors. Therefore, a better understanding of the underlying mechanisms may offer novel approaches for G-CSF-mediated therapeutics. Our previous studies have identified an essential role of Plg in HPSC mobilization from bone marrow (BM) in response to G-CSF. Here, we investigate the role of Plg in G-CSF-stimulated cardiac repair after MI. Our data show that G-CSF significantly improves cardiac repair including increasing neovascularization in the infarct area, and improving ejection fraction and LV internal diameter determined by echocardiogram in WT mice. No improvement on heart function is observed in Plg -/- mice, indicating Plg is required for G-CSF-regulated cardiac repair after MI. To investigate whether Plg regulates HPSC recruitment to the ischemic area, BM transplantation with EGFP-expressing BM cells was performed to visualize BM-derived stem cells in infarcted tissue. Our data show that G-CSF dramatically increases recruitment of GFP + cKit + cells (by 12 fold) in WT mice but not in Plg -/- mice. In addition, BM stem cell-derived vessels and arteries are infrequent in Plg -/- mice suggesting that Plg enhances cardiac repair by promoting stem cell recruitment to the lesion. In further studies, we investigated the role of Plg in the regulation of SDF-1/CXCR-4 axis, a major regulator for HPSC recruitment. Our results show that G-CSF significantly increases CXCR-4 expression in the infarcted area in WT mice. While G-CSF-induced CXCR-4 expression is markedly decreased (80%) in Plg -/- mice, suggesting Plg may regulate CXCR-4 expression during HSPC recruitment to injured heart. Interestingly, Plg does not affect SDF-1 expression in response to G-CSF treatment. Taken together, our findings have identified a critical role of Plg in HSPC recruitment to the lesion site and subsequent tissue repair after MI. Thus, targeting Plg may offer a new therapeutic strategy to improve G-CSF-mediated cardiac repair after MI.

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.

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