The winding road to regenerating the human heart

Gerbin, Kaytlyn A.; Murry, Charles E.

doi:10.1016/j.carpath.2015.02.004

Cited by 100 publications

(83 citation statements)

References 79 publications

(82 reference statements)

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“…The adult heart hosts a limited number of stem and progenitor cells that exhibit heterogeneous characteristics and fates and have therapeutic potential for cardiac repair and regeneration (1). Multiple methods have been applied to the prospective isolation of putative stem and progenitor cells from heart tissue.…”

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confidence: 99%

Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia

Barile¹,

Milano²,

Vassalli³

2017

Stem Cell Investig.

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When injected into acutely infarcted rodent or pig hearts, naturally secreted nanovesicles known as exosomes from cardiac-derived progenitor cells (CPCs) reduce scar size and improve cardiac function. In this regard, exosomes fully mimic the benefits of injecting their parent cells. This recognition paves the way to the development of exosome-based, cell-free treatments for heart disease that could possibly supplant cellbased therapies. Mechanisms of benefit of these vesicles are incompletely understood but cytoprotection, stimulation of angiogenesis, induction of antifibrotic cardiac fibroblasts, and modulation of M1/M2 polarization of macrophages infiltrating the infarcted region can all play important roles. Accordingly, the beneficial molecules carried by CPC-secreted exosomes have been identified only in part but cytoprotective and proangiogenic microRNAs (miRNA) and proteins have been described. Besides CPC-secreted exosomes, vesicles released from other cell types including mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iSPCs) have also been associated with cardioprotection. This review aims to discuss recent advances in our understanding of the role of secreted vesicles in cardiac repair, with a focus on CPC-derived exosomes.

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mentioning

confidence: 99%

Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia

Barile¹,

Milano²,

Vassalli³

2017

Stem Cell Investig.

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“…This landmark study demonstrated the feasibility of producing clinical-grade ESC-derived cardiac progenitor cells and represents the first clinical application of this approach in the setting of HF, but additional studies are necessary to evaluate its safety and efficacy. Although the capacity of ESCs to differentiate toward the cardiac lineages is well established, numerous challenges remain for the clinical implementation of ESCbased therapies [48,49]. For example, allogeneic ESCs face immunological challenges that might require life-long immunosuppression; theoretically autologous iPSC-derived cardiomyocytes circumvent this issue.…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics

2017

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Heart failure (HF), a common sequela of cardiovascular diseases, remains a staggering clinical problem, associated with high rates of morbidity and mortality worldwide. Advances in pharmacological, interventional, and operative management have improved patient care, but these interventions are insufficient to halt the progression of HF, particularly the end-stage irreversible loss of functional cardiomyocytes. Innovative therapies that could prevent HF progression and improve the function of the failing heart are urgently needed. Following successful preclinical studies, two main strategies have emerged as potential solutions: cardiac gene therapy and cardiac regeneration through stem and precursor cell transplantation. Many potential gene-and cell-based therapies have entered into clinical studies, intending to ameliorate cardiac dysfunction in patients with advanced HF. In this review, we focus on the recent advances in cell-and gene-based therapies in the context of cardiovascular disease, emphasizing the most advanced therapies. The principles and mechanisms of action of gene and cell therapies for HF are discussed along with the limitations of current approaches. Finally, we highlight the emerging technologies that hold promise to revolutionize the biological therapies for cardiovascular diseases. STEM CELLS 2017;35:1131-1140 SIGNIFICANCE STATEMENTInnovative therapies that could treat heart failure and improve the function of failing hearts are urgently needed. Following successful preclinical studies, two main strategies have emerged as potential solutions: cardiac gene therapy and cardiac regeneration through stem and precursor cell transplantation. Many gene-and cell-based therapies have entered into clinical studies, intending to ameliorate cardiac dysfunction in patients with advanced HF. In this review, we focus on the recent advances in cell-and gene-based therapies in the context of cardiovascular disease, emphasizing the most advanced therapies that have entered the clinical arena.

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“…Catechins and polyphenols have some antiapoptotic activity through the PI3K/Akt signaling pathway and should be considered as complementary treatments [59]. Cardiac stem cell therapy either stimulating cardiac progenitors or by local or systemic infusion of autologous or heterologous stem cells is a promising therapy [60,61].…”

Section: Future Perspectivesmentioning

confidence: 99%

Alcoholic Cardiomyopathy: Old and New Insights

Fernández‐Solà¹,

Riba²

2017

J Alcohol Drug Depend

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Alcohol cardiomyopathy (ACM) is a chronic dilated heart disease with decreased left ventricular ejection fraction that may be detected in one-fourth of high-dose alcohol consumers. It causes progressive diastolic and systolic dysfunction, supra and ventricular arrhythmias leading to heart failure and increased mortality. The main etiological factor for ACM is ethanol consumption that affects the myocardium in a dose-dependent manner. The mechanisms of ACM are diverse, synchronic and synergistic. Alcohol alters the channel and receptor structure of the cell membrane, decreases intracellular calcium transients, increases oxidative and inflammatory damage, decreases structural protein synthesis and interferes with excitation-contraction coupling mechanisms. Subjects with excessive alcohol consumption may have a subclinical cardiomyopathy with atrial and LV diastolic dysfunction measured by echocardiography or cardiac MR. Subclinical LV dysfunction may progress and later appear clinical features of heart failure. Cardiac myocytes adapt to ethanol aggression by cell and nuclear hypertrophy and dilatation of heart chambers. Progressive myocyte structure disarray and apoptosis produce myocyte loss, hypertrophy of the remaining cells, subendocardial and interstitial fibrosis and low-degree myocyte regeneration. In addition, ethanol also interferes with cardiac repair and adaptation mechanisms. Thus, local cardiomyokines (FGF-21) and growth factors (myostatin, IGF-1, leptin) are modified by ethanol, limiting cardiac remodeling and myocyte regeneration, and leading to abnormal hypertrophy and eccentric ventricle dilatation. This imbalance between aggression and protection mechanisms induces progressive myocyte loss and heart dysfunction. Alcohol abstention is the main goal in ACM, although control drinking (<-60 g/day) may allow recovery of LV function. Monitoring of systemic mediated alcohol-damage, and correction of vitamin and ion deficiencies is needed. Heart failure in ACM should be treated similar to other dilated cardiomyopathies. Heart transplantation is limited to subjects without other organ damage who are able to abstain from alcohol. New preventive and therapeutic strategies are under development to decrease alcohol-mediated myocyte damage and increase heart protective and repair mechanisms.

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The winding road to regenerating the human heart

Cited by 100 publications

References 79 publications

Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia

Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics

Alcoholic Cardiomyopathy: Old and New Insights

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