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 Stem cell-derived cell sheet transplantation for heart tissue repair in myocardial infarction

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Rui Guo ◽  
Masatoshi Morimatsu ◽  
Tian Feng ◽  
Feng Lan ◽  
Dehua Chang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Tissue Repair ◽  
Cardiac Tissue ◽  
Cell Sheet ◽  
Clinical Manifestations ◽  
Induced Pluripotent Stem Cell ◽  
Heart Tissue ◽  
Therapeutic Effects ◽  
Cell Sheets

AbstractStem cell-derived sheet engineering has been developed as the next-generation treatment for myocardial infarction (MI) and offers attractive advantages in comparison with direct stem cell transplantation and scaffold tissue engineering. Furthermore, induced pluripotent stem cell-derived cell sheets have been indicated to possess higher potential for MI therapy than other stem cell-derived sheets because of their capacity to form vascularized networks for fabricating thickened human cardiac tissue and their long-term therapeutic effects after transplantation in MI. To date, stem cell sheet transplantation has exhibited a dramatic role in attenuating cardiac dysfunction and improving clinical manifestations of heart failure in MI. In this review, we retrospectively summarized the current applications and strategy of stem cell-derived cell sheet technology for heart tissue repair in MI.

scholarly journals Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Zhang ◽  
Xin-xing Wan ◽  
Xi-min Hu ◽  
Wen-juan Zhao ◽  
Xiao-xia Ban ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Stem Cell ◽  
Programmed Cell Death ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Effects ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Wide Range

Stem cell therapies have shown promising therapeutic effects in restoring damaged tissue and promoting functional repair in a wide range of human diseases. Generations of insulin-producing cells and pancreatic progenitors from stem cells are potential therapeutic methods for treating diabetes and diabetes-related diseases. However, accumulated evidence has demonstrated that multiple types of programmed cell death (PCD) existed in stem cells post-transplantation and compromise their therapeutic efficiency, including apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Understanding the molecular mechanisms in PCD during stem cell transplantation and targeting cell death signaling pathways are vital to successful stem cell therapies. In this review, we highlight the research advances in PCD mechanisms that guide the development of multiple strategies to prevent the loss of stem cells and discuss promising implications for improving stem cell therapy in diabetes and diabetes-related diseases.

scholarly journals Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1520
Author(s):  
Jieting Wang ◽  
Luying Yu ◽  
Ao Zhou ◽  
Jie Liu ◽  
Kai Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Viral Vectors ◽  
Cardiac Tissue ◽  
Delivery Systems ◽  
Cardiac Cells ◽  
Viral Gene ◽  
Therapeutic Effects ◽  
Cardiac Diseases ◽  
Gene Therapies

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Conventional therapies involving surgery or pharmacological strategies have shown limited therapeutic effects due to a lack of cardiac tissue repair. Gene therapy has opened an avenue for the treatment of cardiac diseases through manipulating the underlying gene mechanics. Several gene therapies for cardiac diseases have been assessed in clinical trials, while the clinical translation greatly depends on the delivery technologies. Non-viral vectors are attracting much attention due to their safety and facile production compared to viral vectors. In this review, we discuss the recent progress of non-viral gene therapies for the treatment of cardiovascular diseases, with a particular focus on myocardial infarction (MI). Through a summary of delivery strategies with which to target cardiac tissue and different cardiac cells for MI treatment, this review aims to inspire new insights into the design/exploitation of non-viral delivery systems for gene cargos to promote cardiac repair/regeneration.

scholarly journals Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-30 ◽  
Author(s):  
Ankit Tandon ◽  
Sangh Jyoti Singh ◽  
Rajnish Kumar Chaturvedi
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Therapeutic Effects ◽  
Potential Candidate ◽  
Behavioral Deficits ◽  
Cell Therapies ◽  
Proliferation And Differentiation

Alzheimer’s disease (AD) and multiple sclerosis are major neurodegenerative diseases, which are characterized by the accumulation of abnormal pathogenic proteins due to oxidative stress, mitochondrial dysfunction, impaired autophagy, and pathogens, leading to neurodegeneration and behavioral deficits. Herein, we reviewed the utility of plant polyphenols in regulating proliferation and differentiation of stem cells for inducing brain self-repair in AD and multiple sclerosis. Firstly, we discussed the genetic, physiological, and environmental factors involved in the pathophysiology of both the disorders. Next, we reviewed various stem cell therapies available and how they have proved useful in animal models of AD and multiple sclerosis. Lastly, we discussed how polyphenols utilize the potential of stem cells, either complementing their therapeutic effects or stimulating endogenous and exogenous neurogenesis, against these diseases. We suggest that polyphenols could be a potential candidate for stem cell therapy against neurodegenerative disorders.

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.

scholarly journals Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson’s Disease

2018 ◽  
Vol 27 (3) ◽  
pp. 456-470 ◽  
Author(s):  
Kang Chi ◽  
Ru-Huei Fu ◽  
Yu-Chuen Huang ◽  
Shih-Yin Chen ◽  
Ching-Ju Hsu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Mouse Model ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells ◽  
Stem Cell Therapies ◽  
Dopaminergic Cell ◽  
Cell Therapies

Parkinson’s disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

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.

Potential Mechanisms Underlying Therapeutic Benefits of Stem Cell for Heart Failure

Nano LIFE ◽  
2019 ◽  
Vol 09 (03) ◽  
pp. 1941004
Author(s):  
Xin Xiong ◽  
Feby Savira ◽  
Kevin W Huang ◽  
Zuoren Yu ◽  
Bing Hui Wang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Disease ◽  
Cardiac Tissue ◽  
Heart Diseases ◽  
Cardiac Cells ◽  
Therapeutic Benefits ◽  
Disease Therapy ◽  
Underlying Mechanisms

Stem cell therapy has been tested for cardiac disease therapy for decades. Initially, researchers only considered stem cells’ differentiative ability to repair damaged cardiac tissue. However, studies have now uncovered novel mechanisms contributing to stem cell healing properties to repair injured cardiac tissue, including via paracrine signaling and exosome secretions, leading to amelioration of cardiac remodeling and enhancement of proliferation, regeneration and survival of stem cell-derived cardiac cells. Understanding these underlying mechanisms could help researchers utilize stem cells as a therapeutic strategy for cardiac disease effectively and address the current limitations, mainly surrounding its survival and differentiative ability in the cardiac milieu. This review will discuss the known potential mechanisms underlying the role of stem cells in contributing to and for the treatment of heart diseases.

scholarly journals Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

2021 ◽  
Vol 22 (15) ◽  
pp. 7813
Author(s):  
Lindsay Kraus ◽  
Chris Bryan ◽  
Marcus Wagner ◽  
Tabito Kino ◽  
Melissa Gunchenko ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Histone Modification ◽  
Epigenetic Regulation ◽  
Critical Role ◽  
Proliferative Potential ◽  
Therapeutic Effects ◽  
Histone 3

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

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