scholarly journals A New Paradigm in Cardiac Regeneration: The Mesenchymal Stem Cell Secretome

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Clara Gallina ◽  
Valentina Turinetto ◽  
Claudia Giachino
Keyword(s):  
Tissue Repair ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Cardiac Regeneration ◽  
Heart Tissue ◽  
Trophic Factors ◽  
Preclinical Models ◽  
New Paradigm ◽  
Great Expectations ◽  
The Subject

The potentialities to apply mesenchymal stem cells (MSCs) in regenerative medicine have been extensively studied over the last decades. In the cardiovascular disease (CVD) field, MSCs-based therapy is the subject of great expectations. Its therapeutic potential has been already shown in several preclinical models and both the safety and efficacy of MSCs-based therapy are being evaluated in humans. It is now clear that the predominant mechanism by which MSCs participate in heart tissue repair is through a paracrine activity. Via the production of a multitude of trophic factors endowed with different properties, MSCs can reduce tissue injury, protect tissue from further adverse effects, and enhance tissue repair. The present review discusses the current understanding of the MSCs secretome as a therapy for treatment of CVD. We provide insights into the possible employment of the MSCs secretome and their released extracellular vesicles as novel approaches for cardiac regeneration that would have certain advantages over injection of living cells.

scholarly journals Strategies to Enhance Mesenchymal Stem Cell-Based Therapies for Acute Respiratory Distress Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jibin Han ◽  
Yanmin Li ◽  
Yuanyuan Li
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Stem Cell ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Therapeutic Potential ◽  
Large Body ◽  
Acute Onset ◽  
Trophic Factors ◽  
Preclinical Models

Acute respiratory distress syndrome (ARDS) is a multifaced disease characterized by the acute onset of hypoxemia, worsened pulmonary compliance, and noncardiogenic pulmonary edema. Despite over five decades of research, specific treatments for established ARDS are still lacking. MSC-based therapies have the advantage of targeting nearly all pathophysiological components of ARDS by means of a variety of secreted trophic factors, exerting anti-inflammatory, antioxidative, immunomodulatory, antiapoptotic, and proangiogenic effects, resulting in significant structural and functional recovery following ARDS in various preclinical models. However, the therapeutic efficacy of transplanted MSCs is limited by their poor engraftment and low survival rate in the injured tissues, major barriers to clinical translation. Accordingly, several strategies have been explored to improve MSC retention in the lung and enhance the innate properties of MSCs in preclinical models of ARDS. To provide a comprehensive and updated view, we summarize a large body of experimental evidence for a variety of strategies directed towards strengthening the therapeutic potential of MSCs in ARDS.

scholarly journals PTX3 Regulation of Inflammation, Hemostatic Response, Tissue Repair, and Resolution of Fibrosis Favors a Role in Limiting Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrea Doni ◽  
Alberto Mantovani ◽  
Barbara Bottazzi ◽  
Remo Castro Russo
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Life Quality ◽  
Unknown Origin ◽  
Protective Role

PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, rapidly produced at inflammatory sites by phagocytes and stromal cells in response to infection or tissue injury. PTX3 interacts with microbial moieties and selected pathogens, with molecules of the complement and hemostatic systems, and with extracellular matrix (ECM) components. In wound sites, PTX3 interacts with fibrin and plasminogen and favors a timely removal of fibrin-rich ECM for an efficient tissue repair. Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown origin, associated with excessive ECM deposition affecting tissue architecture, with irreversible loss of lung function and impact on the patient’s life quality. Maccarinelli et al. recently demonstrated a protective role of PTX3 using the bleomycin (BLM)-induced experimental model of lung fibrosis, in line with the reported role of PTX3 in tissue repair. However, the mechanisms and therapeutic potential of PTX3 in IPF remained to be investigated. Herein, we provide new insights on the possible role of PTX3 in the development of IPF and BLM-induced lung fibrosis. In mice, PTX3-deficiency was associated with worsening of the disease and with impaired fibrin removal and subsequently increased collagen deposition. In IPF patients, microarray data indicated a down-regulation of PTX3 expression, thus suggesting a potential rational underlying the development of disease. Therefore, we provide new insights for considering PTX3 as a possible target molecule underlying therapeutic intervention in IPF.

scholarly journals Repair Injured Heart by Regulating Cardiac Regenerative Signals

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Wen-Feng Cai ◽  
Guan-Sheng Liu ◽  
Lei Wang ◽  
Christian Paul ◽  
Zhi-Li Wen ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Heart Diseases ◽  
Cardiac Regeneration ◽  
Heart Tissue ◽  
Cardiomyocyte Proliferation ◽  
Proliferation Capacity ◽  
End Stage

Cardiac regeneration is a homeostatic cardiogenic process by which the sections of malfunctioning adult cardiovascular tissues are repaired and renewed employing a combination of both cardiomyogenesis and angiogenesis. Unfortunately, while high-quality regeneration can be performed in amphibians and zebrafish hearts, mammalian hearts do not respond in kind. Indeed, a long-term loss of proliferative capacity in mammalian adult cardiomyocytes in combination with dysregulated induction of tissue fibrosis impairs mammalian endogenous heart regenerative capacity, leading to deleterious cardiac remodeling at the end stage of heart failure. Interestingly, several studies have demonstrated that cardiomyocyte proliferation capacity is retained in mammals very soon after birth, and cardiac regeneration potential is correspondingly preserved in some preadolescent vertebrates after myocardial infarction. There is therefore great interest in uncovering the molecular mechanisms that may allow heart regeneration during adult stages. This review will summarize recent findings on cardiac regenerative regulatory mechanisms, especially with respect to extracellular signals and intracellular pathways that may provide novel therapeutics for heart diseases. Particularly, bothin vitroandin vivoexperimental evidences will be presented to highlight the functional role of these signaling cascades in regulating cardiomyocyte proliferation, cardiomyocyte growth, and maturation, with special emphasis on their responses to heart tissue injury.

scholarly journals Therapeutic Potential of Mesenchymal Stem Cells in Regenerative Medicine

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Devang M. Patel ◽  
Jainy Shah ◽  
Anand S. Srivastava
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Genetic Disorders ◽  
Repair Process ◽  
Attractive Candidate

Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expandedin vitro. Moreover, their ability to modulate immune responses makes them an even more attractive candidate for regenerative medicine as allogeneic transplant of these cells is feasible without a substantial risk of immune rejection. MSCs secrete various immunomodulatory molecules which provide a regenerative microenvironment for a variety of injured tissues or organ to limit the damage and to increase self-regulated tissue regeneration. Autologous/allogeneic MSCs delivered via the bloodstream augment the titers of MSCs that are drawn to sites of tissue injury and can accelerate the tissue repair process. MSCs are currently being tested for their potential use in cell and gene therapy for a number of human debilitating diseases and genetic disorders. This paper summarizes the current clinical and nonclinical data for the use of MSCs in tissue repair and potential therapeutic role in various diseases.

ИЗМЕНЕНИЕ ПАРАДИГМЫ МЕТОДОЛОГИИ ЮРИСПРУДЕНЦИИ

2019 ◽  
Vol 13 ◽  
pp. 32-40
Author(s):  
Ю. М. Оборотов
Keyword(s):  
Legal Theory ◽  
Research Strategy ◽  
The State ◽  
New Paradigm ◽  
Methodological Question ◽  
Modern Development ◽  
Decisive Importance ◽  
The Subject ◽  
Methodological Approaches ◽  
The Law

В современной методологии юриспруденции происходит переход от изучения состо­яний ее объекта, которыми выступают право и государство, к постижению этого объек­та в его изменениях и превращениях. Две подсистемы методологии юриспруденции, подсистема обращенная к состоянию права и государства; и подсистема обращенная к изменениям права и государства, — получают свое отображение в концептуальной форме, методологических подходах, методах, специфических понятиях. Показательны перемены в содержании методологии юриспруденции, где определяю­щее значение имеют методологические подходы, определяющие стратегию исследова­тельских поисков во взаимосвязи юриспруденции с правом и государством. Среди наи­более характерных подходов антропологический, аксиологический, цивилизационный, синергетический и герменевтический — определяют плюралистичность современной методологии и свидетельствуют о становлении новой парадигмы методологии юриспру­денции.   In modern methodology of jurisprudence there is a transition from the study the states of its object to its comprehension in changes and transformations. Hence the two subsystems of methodology of jurisprudence: subsystem facing the states of the law and the state as well as their components and aspects; and subsystem facing the changes of the law and the state in general and their constituents. These subsystems of methodology of jurisprudence receive its reflection in conceptual form, methodological approaches, methods, specific concepts. Methodology of jurisprudence should not be restricted to the methodology of legal theory. In this regard, it is an important methodological question about subject of jurisprudence. It is proposed to consider the subject of jurisprudence as complex, covering both the law and the state in their specificity, interaction and integrity. Indicative changes in the content methodology of jurisprudence are the usage of decisive importance methodological approaches that govern research strategy searches in conjunction with the law and the state. Among the most characteristic of modern development approaches: anthropological, axiological, civilization, synergistic and hermeneutic. Modern methodology of jurisprudence is pluralistic in nature alleging various approaches to the law and the state. Marked approaches allow the formation of a new paradigm methodology of jurisprudence.

scholarly journals Macrophage-Derived Inflammation Induces a Transcriptome Makeover in Mesenchymal Stromal Cells Enhancing Their Potential for Tissue Repair

2021 ◽  
Vol 22 (2) ◽  
pp. 781
Author(s):  
Inés Maldonado-Lasunción ◽  
Nick O’Neill ◽  
Oliver Umland ◽  
Joost Verhaagen ◽  
Martin Oudega
Keyword(s):  
Growth Factor ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Vascular Endothelial ◽  
Glial Derived Neurotrophic Factor ◽  
Transcriptomic Changes ◽  
Endothelial Growth Factor ◽  
Cellular Components ◽  
Hepatocyte Growth ◽  
Go Terms

Pre-clinical and clinical studies revealed that mesenchymal stromal cell (MSC) transplants elicit tissue repair. Conditioning MSC prior to transplantation may boost their ability to support repair. We investigated macrophage-derived inflammation as a means to condition MSC by comprehensively analyzing their transcriptome and secretome. Conditioning MSC with macrophage-derived inflammation resulted in 3208 differentially expressed genes, which were annotated with significantly enriched GO terms for 1085 biological processes, 85 cellular components, and 79 molecular functions. Inflammation-mediated conditioning increased the secretion of growth factors that are key for tissue repair, including vascular endothelial growth factor, hepatocyte growth factor, nerve growth factor and glial-derived neurotrophic factor. Furthermore, we found that inflammation-mediated conditioning induces transcriptomic changes that challenge the viability and mobility of MSC. Our data support the notion that macrophage-derived inflammation stimulates MSC to augment their paracrine repair-supporting activity. The results suggest that inflammatory pre-conditioning enhances the therapeutic potential of MSC transplants.

scholarly journals Cell Therapy in Ischemic Heart Disease: Interventions That Modulate Cardiac Regeneration

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Maximiliano I. Schaun ◽  
Bruna Eibel ◽  
Melissa Kristocheck ◽  
Grasiele Sausen ◽  
Luana Machado ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cell Therapy ◽  
Ischemic Heart Disease ◽  
Adult Stem Cells ◽  
Therapeutic Potential ◽  
Cardiac Regeneration ◽  
Current Data ◽  
Ischemic Heart ◽  
Promising Alternative ◽  
Clinical Conditions

The incidence of severe ischemic heart disease caused by coronary obstruction has progressively increased. Alternative forms of treatment have been studied in an attempt to regenerate myocardial tissue, induce angiogenesis, and improve clinical conditions. In this context, cell therapy has emerged as a promising alternative using cells with regenerative potential, focusing on the release of paracrine and autocrine factors that contribute to cell survival, angiogenesis, and tissue remodeling. Evidence of the safety, feasibility, and potential effectiveness of cell therapy has emerged from several clinical trials using different lineages of adult stem cells. The clinical benefit, however, is not yet well established. In this review, we discuss the therapeutic potential of cell therapy in terms of regenerative and angiogenic capacity after myocardial ischemia. In addition, we addressed nonpharmacological interventions that may influence this therapeutic practice, such as diet and physical training. This review brings together current data on pharmacological and nonpharmacological approaches to improve cell homing and cardiac repair.

Industrial Factionalism in Modern German History

1991 ◽  
Vol 24 (2-3) ◽  
pp. 122-131 ◽  
Author(s):  
Peter Hayes
Keyword(s):  
Republican Party ◽  
Industrial Revolution ◽  
German History ◽  
Labor Costs ◽  
New Paradigm ◽  
Business World ◽  
Iron And Steel ◽  
Domestic Markets ◽  
Parliamentary Government ◽  
The Subject

At a time when the Republican party in America seems to have abandoned its brief hopes of proclaiming a new paradigm, it may seem apropos to observe that old ones die hard—and not only in public life. A case in point from the scholarly world is the subject of this essay: the persistent historiographical notion of industrial factionalism. Throughout this century, students of German political economy have tended to see the country's business world as divided between two groupings. One comprises the classic heavy industries of the first Industrial Revolution and the Ruhr: coal, iron, and steel. Supposedly oriented toward domestic markets, burdened with high labor costs, doomed to flattening gains in productivity and profits, and habituated to hierarchy within their plants and the nation, executives in this grouping have figured in the historical literature as consistently and intransigently united against free trade, labor unions, and parliamentary government—indeed, against modernization itself.

Quercetin: A Potential Candidate For The Treatment Of Arthritis

2021 ◽  
Vol 21 ◽  
Author(s):  
Ahsas Goyal ◽  
Neetu Agrawal
Keyword(s):  
Rheumatoid Arthritis ◽  
Medicinal Plants ◽  
Therapeutic Potential ◽  
Gouty Arthritis ◽  
Potential Candidate ◽  
Protective Effects ◽  
Preclinical Models ◽  
Healthy Life ◽  
Health Promoting ◽  
Dietary Component

: Diet plays a significant role in ensuring healthy life and the bioactive compounds present in food and medicinal plants may be developed as drugs that combat various illnesses. A bioactive flavanoid, quercetin which is a dietary component possesses numerous health-promoting effects. In preclinical models of rheumatoid arthritis, gouty arthritis and osteoarthritis, quercetin has shown significant joint protective effects. Taking into account the significance of this compound, the present review discusses its anti-arthritic properties, demonstrating its mechanism of action for the treatment of arthritis with its therapeutic potential.

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