-
Frontiers in Endocrinology 2020The β-cell regeneration field has shown a strong knowledge boost in the last 10 years. Pluripotent stem cell differentiation and direct reprogramming from other adult... (Review)
Review
The β-cell regeneration field has shown a strong knowledge boost in the last 10 years. Pluripotent stem cell differentiation and direct reprogramming from other adult cell types are becoming more tangible long-term diabetes therapies. Newly generated β-like-cells consistently show hallmarks of native β-cells and can restore normoglycemia in diabetic mice in virtually all recent studies. Nonetheless, these cells still show important compromises in insulin secretion, cell metabolism, electrical activity, and overall survival, perhaps due to a lack of signal integration from other islet cells. Mounting data suggest that diabetes is not only a β-cell disease, as the other islet cell types also contribute to its physiopathology. Here, we present an update on the most recent studies of islet cell heterogeneity and paracrine interactions in the context of restoring an integrated islet function to improve β-cell replacement therapies.
Topics: Animals; Cell Differentiation; Cell Survival; Diabetes Mellitus; Humans; Insulin-Secreting Cells; Islets of Langerhans; Paracrine Communication; Regeneration
PubMed: 33613453
DOI: 10.3389/fendo.2020.619150 -
American Journal of Physiology. Lung... Jun 2019Both physiological homeostasis and pathological disease processes in the lung typically result from complex, yet coordinated multicellular responses that are... (Review)
Review
Both physiological homeostasis and pathological disease processes in the lung typically result from complex, yet coordinated multicellular responses that are synchronized via paracrine and endocrine intercellular communication pathways. Of late, extracellular vesicles have emerged as important information shuttles that can coordinate and disseminate homeostatic and disease signals. In parallel, extracellular vesicles in biological fluids such as sputum, mucus, epithelial lining fluid, edema fluid, the pulmonary circulation, pleural fluid, and lymphatics have emerged as promising candidate biomarkers for diagnosis and prognosis in lung disease. Extracellular vesicles are small, subcellular, membrane-bound vesicles containing cargos from parent cells such as lipids, proteins, genetic information, or entire organelles. These cargos endow extracellular vesicles with biologically active information or functions by which they can reprogram their respective target cells. Recent studies show that extracellular vesicles found in lung-associated biological fluids play key roles as biomarkers and effectors of disease. Conversely, administration of naïve or engineered extracellular vesicles with homeostatic or reparative effects may provide a promising novel protective and regenerative strategy to treat lung disease. To highlight this rapidly developing field, the is now launching a special Call for Papers on extracellular vesicles in lung health, disease, and therapy. This review aims to set the stage for this call by introducing extracellular vesicles and their emerging roles in lung physiology and pathobiology.
Topics: Biomarkers; Endocrine System; Extracellular Vesicles; Humans; Lung; Lung Diseases; Paracrine Communication; Prognosis
PubMed: 30892076
DOI: 10.1152/ajplung.00546.2018 -
Journal of Gastroenterology and... Aug 2013Cholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are... (Review)
Review
Cholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are nourished by their own arterial supply, the peribiliary plexus. This capillary network originates from the hepatic artery and is strictly arranged around the intrahepatic bile ducts. Biliary and vascular structures are linked by a close anatomic and functional association necessary for liver development, normal organ physiology, and liver repair. This strong association is finely regulated by a range of angiogenic signals, enabling the cross talk between cholangiocytes and the different vascular cell types. This review will briefly illustrate the "vascular" properties of cholangiocytes, their underlying molecular mechanisms and the relevant pathophysiological settings.
Topics: Angiopoietins; Animals; Autocrine Communication; Bile Duct Diseases; Bile Ducts, Intrahepatic; Epithelial Cells; Epithelium; Humans; Liver; Liver Diseases, Alcoholic; Liver Regeneration; Neovascularization, Pathologic; Paracrine Communication; Platelet-Derived Growth Factor; Rats; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 23855292
DOI: 10.1111/jgh.12022 -
Bioscience Trends 2019Stem cells are an undifferentiated cell population that has the ability to develop into many different cell types and also has the ability to repair damaged tissues in... (Review)
Review
Stem cells are an undifferentiated cell population that has the ability to develop into many different cell types and also has the ability to repair damaged tissues in some cases. For a long time, the stem cell regenerative paradigm has been based on the assumption that progenitor cells play a critical role in tissue repair by means of their plasticity and differentiation potential. However, recent works suggest that the mechanism underlying the benefits of stem cell transplantation might relate to a paracrine modulatory effect rather than the replacement of affected cells at the site of injury. This paracrine modulatory effect derives from secretome which comprises a diverse host of growth factors, cytokines, chemokines, angiogenic factors, and exosomes which are extracellular vesicles that are produced in the endosomal compartment of most eukaryotic cells and are from about 30 to several hundred nanometers in diameter. The role of these factors is being increasingly recognized as key to the regulation of many physiological processes including leading endogenous and progenitor cells to sites of injury as well as mediating apoptosis, proliferation, migration, and angiogenesis. In reality, the immunomodulatory and paracrine role of these factors may mainly account for the therapeutic effects of stem cells and a number of in vitro and in vivo researches have proved limited stem cell engraftment at the site of injury. As a cell-free way for regenerative medicine therapies, stem cell secretome has shown great potential in a variety of clinical applications including prevention of cardiac disfunction, neurodegenerative disease, type 1 diabetes, hair loss, tumors, and joint osteoarthritis.
Topics: Extracellular Vesicles; Humans; Immunomodulation; Paracrine Communication; Regenerative Medicine; Stem Cell Transplantation; Stem Cells
PubMed: 31527327
DOI: 10.5582/bst.2019.01226 -
BioMed Research International 2015Cysteinyl leukotrienes (cysLTs) are cell membrane-impermeant lipid mediators that play major roles in the pathogenesis of eosinophilic inflammation and are recognized to... (Review)
Review
Cysteinyl leukotrienes (cysLTs) are cell membrane-impermeant lipid mediators that play major roles in the pathogenesis of eosinophilic inflammation and are recognized to act via at least 2 receptors, namely, cysLT1 receptor (cysLT1R) and cysLT2 receptor (cysLT2R). Eosinophils, which are granulocytes classically associated with host defense against parasitic helminthes and allergic conditions, are distinguished from leukocytes by their dominant population of cytoplasmic crystalloid (also termed secretory, specific, or secondary) granules that contain robust stores of diverse preformed proteins. Human eosinophils are the main source of cysLTs and are recognized to express both cysLTs receptors (cysLTRs) on their surface, at the plasma membrane. More recently, we identified the expression of cysLTRs in eosinophil granule membranes and demonstrated that cysLTs, acting via their granule membrane-expressed receptors, elicit secretion from cell-free human eosinophil granules. Herein, we review the multifaceted roles of cysLTs in eliciting eosinophil granule protein secretion. We discuss the intracrine and autocrine/paracrine secretory responses evoked by cysLTs in eosinophils and in cell-free extracellular eosinophil crystalloid granules. We also discuss the importance of this finding in eosinophil immunobiology and speculate on its potential role(s) in eosinophilic diseases.
Topics: Animals; Autocrine Communication; Cell Membrane; Eosinophils; Gene Expression Regulation; Humans; Leukotrienes; Paracrine Communication; Receptors, Leukotriene; Secretory Vesicles
PubMed: 25866815
DOI: 10.1155/2015/848762 -
International Journal of Oncology Jun 2014Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific... (Review)
Review
Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific stem cells to rebuild damaged tissue and cancer stem cells to initiate and promote cancer. Mesenchymal stem cells, attracted to wounds and cancer, facilitate wound healing and support cancer progression primarily by secreting bioactive factors. There is now growing evidence that, like mesenchymal stem cells, also tissue-specific and cancer stem cells manipulate their environment by paracrine actions. Soluble factors and microvesicles released by these stem cells have been shown to protect recipient cells from apoptosis and to stimulate neovascularization. These paracrine mechanisms may allow stem cells to orchestrate wound healing and cancer progression. Hence, understanding these stem cell-driven paracrine effects may help to improve tissue regeneration and cancer treatment.
Topics: Animals; Apoptosis; Humans; Mesenchymal Stem Cells; Neoplasms; Neoplastic Stem Cells; Neovascularization, Pathologic; Organ Specificity; Paracrine Communication; Signal Transduction; Wound Healing
PubMed: 24728412
DOI: 10.3892/ijo.2014.2385 -
Stem Cell Reviews and Reports Dec 2022Mesenchymal stem cell (MSC) therapy has gained significant traction in the context of cardiovascular repair, and have been proposed to exert their regenerative effects... (Review)
Review
Mesenchymal stem cell (MSC) therapy has gained significant traction in the context of cardiovascular repair, and have been proposed to exert their regenerative effects via the secretion of paracrine factors. In this systematic review, we examined the literature and consolidated available evidence for the "paracrine hypothesis". Two Ovid SP databases were searched using a strategy encompassing paracrine mediated MSC therapy in the context of ischemic heart disease. This yielded 86 articles which met the selection criteria for inclusion in this study. We found that the MSCs utilized in these articles were primarily derived from bone marrow, cardiac tissue, and adipose tissue. We identified 234 individual protective factors across these studies, including VEGF, HGF, and FGF2; which are proposed to exert their effects in a paracrine manner. The data collated in this systematic review identifies secreted paracrine factors that could decrease apoptosis, and increase angiogenesis, cell proliferation, and cell viability. These included studies have also demonstrated that the administration of MSCs and indirectly, their secreted factors can reduce infarct size, and improve left ventricular ejection fraction, contractility, compliance, and vessel density. Furthering our understanding of the way these factors mediate repair could lead to the identification of therapeutic targets for cardiac regeneration.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Paracrine Communication; Cardiovascular Diseases; Stroke Volume; Myocardial Infarction; Ventricular Function, Left
PubMed: 35896860
DOI: 10.1007/s12015-022-10429-6 -
Antioxidants & Redox Signaling Mar 2021Perivascular adipose tissue (PVAT), which is present surrounding most blood vessels, from the aorta to the microvasculature of the dermis, is mainly composed of fat... (Review)
Review
Perivascular adipose tissue (PVAT), which is present surrounding most blood vessels, from the aorta to the microvasculature of the dermis, is mainly composed of fat cells, fibroblasts, stem cells, mast cells, and nerve cells. Although the PVAT is objectively present, its physiological and pathological significance has long been ignored. PVAT was considered as a supporting component of blood vessels and a protective cushion to the vessel wall from the neighboring tissues during relaxation and contraction. Nonetheless, further extensive research found that PVAT actively regulates blood vessel tone through PVAT-derived vasoactive factors, including both relaxing and contracting factors. In addition, PVAT contributes to atherosclerosis through paracrine secretion of a large number of bioactive factors such as adipokines and cytokines. Thereby, PVAT regulates the functions of blood vessels through various mechanisms operating directly on PVAT or on the underlying vessel layers, including vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). PVAT is a unique adipose tissue that plays an essential role in maintaining the vascular structure and regulating vascular function and homeostasis. This review focuses on recent updates on the various PVAT roles in hypertension and atherosclerosis. Future studies should further investigate the actual contribution of alterations in PVAT metabolism to the overall systemic outcomes of cardiovascular disease, which remains largely unknown. In addition, the messengers and underlying mechanisms responsible for the crosstalk between PVAT and ECs and VSMCs in the vascular wall should be systematically addressed, as well as the contributions of PVAT aging to vascular dysfunction.
Topics: Adipose Tissue; Animals; Atherosclerosis; Blood Vessels; Endothelial Cells; Humans; Hypertension; Muscle Cells; Muscle, Smooth, Vascular; Paracrine Communication
PubMed: 32390459
DOI: 10.1089/ars.2020.8103 -
Cells Aug 2021For multi-cellular organisms to organize tissues, their cells must communicate with each other [...].
For multi-cellular organisms to organize tissues, their cells must communicate with each other [...].
Topics: Animals; Autocrine Communication; Fibroblast Growth Factors; Humans; Neoplasms; Paracrine Communication; Receptors, Fibroblast Growth Factor; Signal Transduction
PubMed: 34571880
DOI: 10.3390/cells10092231 -
Drug Discovery Today Aug 2021Aging and pre-existing conditions in older patients increase severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severity and its complications, although the... (Review)
Review
Aging and pre-existing conditions in older patients increase severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severity and its complications, although the causes remain unclear. Apart from acute pulmonary syndrome, Coronavirus 2019 (COVID-19) can increasingly induce chronic conditions. Importantly, SARS-CoV-2 triggers de novo type 2 diabetes mellitus (T2DM) linked to age-associated cardiovascular disease (CVD), cancers, and neurodegeneration. Mechanistically, SARS-CoV-2 induces inflammation, possibly through damage-associated molecular pattern (DAMP) signaling and 'cytokine storm,' causing insulin resistance and the adiponectin (APN) paradox, a phenomenon linking metabolic dysfunction to chronic disease. Accordingly, preventing the APN paradox by suppressing APN-related inflammatory signaling might prove beneficial. A better understanding could uncover novel therapies for SARS-CoV-2 and its chronic disorders.
Topics: Adiponectin; Aging; COVID-19; Chronic Disease; Diabetes Mellitus, Type 2; Humans; Inflammation; Paracrine Communication; SARS-CoV-2
PubMed: 33775925
DOI: 10.1016/j.drudis.2021.03.013