scholarly journals The Immunomodulatory Properties of Extracellular Vesicles Derived from Probiotics: A Novel Approach for the Management of Gastrointestinal Diseases

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1038 ◽  
Author(s):  
Jose Alberto Molina-Tijeras ◽  
Julio Gálvez ◽  
Maria Elena Rodríguez-Cabezas
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Intestinal Barrier ◽  
Cell Types ◽  
Gastrointestinal Diseases ◽  
Host Interactions ◽  
Beneficial Effects ◽  
Novel Approach ◽  
Probiotic Strains ◽  
Different Cell Types

Probiotics, included in functional foods, nutritional supplements, or nutraceuticals, exhibit different beneficial effects on gut function. They are extensively used to improve the digestive processes as well as reduce the symptoms and progression of different diseases. Probiotics have shown to improve dysbiosis and modulate the immune response of the host by interacting with different cell types. Probiotics and the host can interact in a direct way, but it is becoming apparent that communication occurs also through extracellular vesicles (EVs) derived from probiotics. EVs are key for bacteria–bacteria and bacteria–host interactions, since they carry a wide variety of components that can modulate different signaling pathways, including those involved in the immune response. Interestingly, EVs are recently starting to be considered as an alternative to probiotics in those cases for which the use of live bacteria could be dangerous, such as immunocompromised individuals or situations where the intestinal barrier is impaired. EVs can spread through the mucus layer and interact with the host, avoiding the risk of sepsis. This review summarizes the existing knowledge about EVs from different probiotic strains, their properties, and their potential use for the prevention or treatment of different gastrointestinal diseases.

scholarly journals Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview

2019 ◽  
Vol 20 (10) ◽  
pp. 2534 ◽  
Author(s):  
Núria Piqué ◽  
Mercedes Berlanga ◽  
David Miñana-Galbis
Keyword(s):  
Safety Profile ◽  
Intestinal Barrier ◽  
Antibiotic Resistance Genes ◽  
Allergic Diseases ◽  
Gastrointestinal Diseases ◽  
Beneficial Effects ◽  
Gut Colonization ◽  
Cell Extracts ◽  
Probiotic Strains ◽  
Systemic Infections

Nowadays, the oral use of probiotics is widespread. However, the safety profile with the use of live probiotics is still a matter of debate. Main risks include: Cases of systemic infections due to translocation, particularly in vulnerable patients and pediatric populations; acquisition of antibiotic resistance genes; or interference with gut colonization in neonates. To avoid these risks, there is an increasing interest in non-viable microorganisms or microbial cell extracts to be used as probiotics, mainly heat-killed (including tyndallized) probiotic bacteria (lactic acid bacteria and bifidobacteria). Heat-treated probiotic cells, cell-free supernatants, and purified key components are able to confer beneficial effects, mainly immunomodulatory effects, protection against enteropathogens, and maintenance of intestinal barrier integrity. At the clinical level, products containing tyndallized probiotic strains have had a role in gastrointestinal diseases, including bloating and infantile coli—in combination with mucosal protectors—and diarrhea. Heat-inactivated probiotics could also have a role in the management of dermatological or respiratory allergic diseases. The reviewed data indicate that heat-killed bacteria or their fractions or purified components have key probiotic effects, with advantages versus live probiotics (mainly their safety profile), positioning them as interesting strategies for the management of common prevalent conditions in a wide variety of patients´ characteristics.

scholarly journals NANOmetric BIO-Banked MSC-Derived Exosome (NANOBIOME) as a Novel Approach to Regenerative Medicine

2018 ◽  
Vol 7 (10) ◽  
pp. 357 ◽  
Author(s):  
Bruna Codispoti ◽  
Massimo Marrelli ◽  
Francesco Paduano ◽  
Marco Tatullo
Keyword(s):  
Plasma Membrane ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Cell Types ◽  
Endogenous Factors ◽  
Cell Lineages ◽  
Novel Approach ◽  
Therapeutic Uses ◽  
Technical Issues

Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. In fact, MSCs can differentiate into several cell lineages and show paracrine behavior by releasing endogenous factors that stimulate tissue repair and modulate local immune response. Each MSC type is affected by specific biobanking issues—technical issues as well as regulatory and ethical concerns—thus making it quite tricky to safely and commonly use MSC banking for swift regenerative applications. Extracellular vesicles (EVs) include a group of 150–1000 nm vesicles that are released by budding from the plasma membrane into biological fluids and/or in the culture medium from varied and heterogenic cell types. EVs consist of various vesicle types that are defined with different nomenclature such as exosomes, shedding vesicles, nanoparticles, microvesicles and apoptotic bodies. Ectosomes, micro- and nanoparticles generally refer to the direct release of single vesicles from the plasma membrane. While many studies describe exosomes as deriving from multivesicular bodies, solid evidence about the origin of EVs is often lacking. Extracellular vesicles represent an important portion of the cell secretome. Their numerous properties can be used for diagnostic, prognostic, and therapeutic uses, so EVs are considered to be innovative and smart theranostic tools. The aim of this review is to investigate the usefulness of exosomes as carriers of the whole information panel characterizing the use of MSCs in regenerative medicine. Our purpose is to make a step forward in the development of the NANOmetric BIO-banked MSC-derived Exosome (NANOBIOME).

scholarly journals Cell-Based Therapies for Cardiac Regeneration: A Comprehensive Review of Past and Ongoing Strategies

2018 ◽  
Vol 19 (10) ◽  
pp. 3194 ◽  
Author(s):  
Andrea Ghiroldi ◽  
Marco Piccoli ◽  
Federica Cirillo ◽  
Michelle Monasky ◽  
Giuseppe Ciconte ◽  
...  
Keyword(s):  
Causes Of Death ◽  
Ventricular Dysfunction ◽  
State Of The Art ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Left Ventricular ◽  
Principal Mechanism ◽  
Beneficial Effects ◽  
Clinical Conditions ◽  
Different Cell Types

Despite considerable improvements in the treatment of cardiovascular diseases, heart failure (HF) still represents one of the leading causes of death worldwide. Poor prognosis is mostly due to the limited regenerative capacity of the adult human heart, which ultimately leads to left ventricular dysfunction. As a consequence, heart transplantation is virtually the only alternative for many patients. Therefore, novel regenerative approaches are extremely needed, and several attempts have been performed to improve HF patients’ clinical conditions by promoting the replacement of the lost cardiomyocytes and by activating cardiac repair. In particular, cell-based therapies have been shown to possess a great potential for cardiac regeneration. Different cell types have been extensively tested in clinical trials, demonstrating consistent safety results. However, heterogeneous efficacy data have been reported, probably because precise end-points still need to be clearly defined. Moreover, the principal mechanism responsible for these beneficial effects seems to be the paracrine release of antiapoptotic and immunomodulatory molecules from the injected cells. This review covers past and state-of-the-art strategies in cell-based heart regeneration, highlighting the advantages, challenges, and limitations of each approach.

CF Monocyte Derived Macrophages Have an Attenuated Response to Extracellular Vesicles Secreted by Airway Epithelial Cells

2021 ◽  
Author(s):  
Katja Koeppen ◽  
Amanda B Nymon ◽  
Roxanna Barnaby ◽  
Zhongyou Li ◽  
Thomas H Hampton ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Bacterial Infection ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
Airway Epithelial ◽  
Immune Genes ◽  
Innate Immune Genes

Mutations in CFTR alter macrophage responses, for example, by reducing their ability to phagocytose and kill bacteria. Altered macrophage responses may facilitate bacterial infection and inflammation in the lungs, contributing to morbidity and mortality in cystic fibrosis (CF). Extracellular vesicles (EVs) are secreted by multiple cell types in the lungs and participate in the host immune response to bacterial infection, but the effect of EVs secreted by CF airway epithelial cells (AEC) on CF macrophages is unknown. This report examines the effect of EVs secreted by primary AEC on monocyte derived macrophages (MDM) and contrasts responses of CF and WT MDM. We found that EVs generally increase pro-inflammatory cytokine secretion and expression of innate immune genes in MDM, especially when EVs are derived from AEC exposed to Pseudomonas aeruginosa, and that this effect is attenuated in CF MDM. Specifically, EVs secreted by P. aeruginosa exposed AEC induced immune response genes and increased secretion of pro-inflammatory cytokines, chemoattractants and chemokines involved in tissue repair by WT MDM, but these effects were less robust in CF MDM. We attribute attenuated responses by CF MDM to differences between CF and WT macrophages because EVs secreted by CF AEC or WT AEC elicited similar responses in CF MDM. Our findings demonstrate the importance of AEC EVs in macrophage responses and show that the Phe508del mutation in CFTR attenuates the innate immune response of MDM to EVs.

scholarly journals Extracellular Vesicles in Inflammatory Bowel Disease: Small Particles, Big Players

2020 ◽  
Author(s):  
M Valter ◽  
S Verstockt ◽  
J A Finalet Ferreiro ◽  
I Cleynen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Extracellular Vesicles ◽  
Bowel Disease ◽  
Intestinal Barrier ◽  
Cell Types ◽  
Physiological Status ◽  
Intestinal Epithelial ◽  
Functional Roles ◽  
Physiological Processes ◽  
Inflammatory Bowel

Abstract Extracellular vesicles are nanovesicles released by many cell types into the extracellular space. They are important mediators of intercellular communication, enabling the functional transfer of molecules from one cell to another. Moreover, their molecular composition reflects the physiological status of the producing cell and tissue. Consequently, these vesicles have been involved in many [patho]physiological processes such as immunomodulation and intestinal epithelial repair, both key processes involved in inflammatory bowel disease. Given that these vesicles are present in many body fluids, they also provide opportunities for diagnostic, prognostic, and therapeutic applications. In this review, we summarise functional roles of extracellular vesicles in health and disease, with a focus on immune regulation and intestinal barrier integrity, and review recent studies on extracellular vesicles and inflammatory bowel disease. We also elaborate on their clinical potential in inflammatory bowel disease.

Immunological changes accompanying the development of experimental neoplastic process

2015 ◽  
Vol 6 (2) ◽  
pp. 96-108
Author(s):  
Elena Aleksandrovna Dementeva ◽  
Olga Petrovna Gurina
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Genome Stability ◽  
Cell Types ◽  
Transformation Process ◽  
The Body ◽  
Expression Of Genes ◽  
Neoplastic Process ◽  
And Control ◽  
Different Cell Types

The key immunology problem remains the understanding of the mechanisms for the effective protection of the body against various pathogens with simultaneous suppression of the immune response to autoantigens. The pathogenesis of neoplastic pathological processes includes violations of the mechanisms of normal cell growth and cell proliferation. Antitumor immune response is a complex event, involving many different cell types. But despite the ability of the immune system to recognize and respond to a variety of tumor-associated antigens, the neoplastic process overcomes the protective forces of the organism, grows and spreads. For cancer cells characterized by independence from antiproliferative signals, autocrine stimulation of growth disturbances in the system, induction of apoptosis and control of genome stability. As a result of accumulation of genetic and epigenetic changes in tumor cells differ significantly from the normal range and the level of expression of genes involved in the transformation process, the accumulation of mutations in key genes promoters and suppressors of tumorigenesis. This creates the opportunity for recognition by cells of the immune system. The study of changes in value and operation of the various elements of the immune system in the development of experimental neoplastic process allows you to identify the mechanisms of interaction in the system «malignant tumor-immune system, to assess patterns of interaction with other organs and tissues, to create a theoretical pathogenetically reasonable premise for the development of anticancer therapy.

Extracellular vesicles in the circulation: are erythrocyte microvesicles a confounder in the plasma haemoglobin assay?

2013 ◽  
Vol 41 (1) ◽  
pp. 288-292 ◽  
Author(s):  
Karen M.K. de Vooght ◽  
Cedric Lau ◽  
Pim P.M. de Laat ◽  
Richard van Wijk ◽  
Wouter W. van Solinge ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Formation Rate ◽  
Haemoglobin Concentration ◽  
Cell Types ◽  
Total Cell ◽  
Plasma Haemoglobin ◽  
Free Plasma Haemoglobin ◽  
Free Haemoglobin ◽  
Different Cell Types ◽  
Free Plasma

Blood contains a mixture of extracellular vesicles from different cell types, primarily platelets, endothelial cells, leucocytes and erythrocytes. Erythrocytes are the most abundant cell type in blood and could, especially in certain pathologies, represent an important source of vesicles. Since erythrocytes contain the haemoglobin components iron and haem, which are potentially toxic, it is important to investigate the contribution of vesicle-associated haemoglobin to total cell-free haemoglobin levels. To our knowledge, this is the first time that cell-free plasma haemoglobin has been differentiated into vesicle-associated and molecular species. We investigated the contribution of vesicle-associated haemoglobin in residual patient material that was routinely analysed for total cell-free plasma haemoglobin. All patient samples included in the study were haemolytic with total cell-free haemoglobin concentration ranging from 80 to 2500 mg/l. In the majority of the samples, total cell-free haemoglobin concentration was between 100 and 200 mg/l. No haemoglobin could be detected in the vesicle fraction, indicating that the contribution of vesicle-associated haemoglobin to total cell free-haemoglobin levels in plasma is negligible. It is important to investigate whether erythrocyte vesicles are not formed in blood or that their production is not increased during pathologies associated with haemolysis or that the clearance rate of the vesicles surpasses the formation rate.

scholarly journals The Significance of Phenotyping and Quantification of Plasma Extracellular Vesicles Levels Using High-Sensitivity Flow Cytometry during COVID-19 Treatment

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 767
Author(s):  
Igor Kudryavtsev ◽  
Olga Kalinina ◽  
Vadim Bezrukikh ◽  
Olesya Melnik ◽  
Alexey Golovkin
Keyword(s):  
Flow Cytometry ◽  
Extracellular Vesicles ◽  
Dynamic Assessment ◽  
Severe Infection ◽  
High Sensitivity ◽  
Cell Types ◽  
Significant Loss ◽  
Therapy Effectiveness ◽  
Scientific Testing ◽  
Different Cell Types

New investigation results point to the potential participation of extracellular vesicles (EVs) in the pathogenesis of coronavirus infection, its progression, and mechanisms of the therapy effectiveness. This dictates the necessity to transfer scientific testing technologies to medical practice. Here, we demonstrated the method of phenotyping and quantitative analysis of plasma EVs based on differential centrifugation, immunostaining, and high-sensitivity multicolor flow cytometry. We used EV markers that were potentially associated with SARS-CoV-2 dissemination via vesicles and cell-origination markers, characterizing objects from different cell types that could influence clinical manifestation of COVID-19. Plasma levels of CD235a+ and CD14+ EVs in patients with moderate infection were significantly increased while CD8+ and CD19+ EVs were decreased comparing with HD. Patients with severe infection had lower levels of CD4+, CD19+, and CD146+ EVs than HD. These findings demonstrate that EV concentrations in COVID-19 are severity related. Moreover, the three-point dynamic assessment demonstrated significant loss of CD63+ and CD147+ plasma EVs. The used method can be a convenient tool for vital infection pathogenesis investigation and for COVID-19 diagnostics.

scholarly journals Targeting S100A4 with niclosamide attenuates inflammatory and profibrotic pathways in models of amyotrophic lateral sclerosis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Martina Milani ◽  
Eleonora Mammarella ◽  
Simona Rossi ◽  
Chiara Miele ◽  
Serena Lattante ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cell Types ◽  
Specific Protein ◽  
Beneficial Effects ◽  
Hexanucleotide Repeat ◽  
Hexanucleotide Repeat Expansion ◽  
Als Patients ◽  
Different Cell Types ◽  
Lateral Sclerosis

Abstract Background An increasing number of studies evidences that amyotrophic lateral sclerosis (ALS) is characterized by extensive alterations in different cell types and in different regions besides the CNS. We previously reported the upregulation in ALS models of a gene called fibroblast-specific protein-1 or S100A4, recognized as a pro-inflammatory and profibrotic factor. Since inflammation and fibrosis are often mutual-sustaining events that contribute to establish a hostile environment for organ functions, the comprehension of the elements responsible for these interconnected pathways is crucial to disclose novel aspects involved in ALS pathology. Methods Here, we employed fibroblasts derived from ALS patients harboring the C9orf72 hexanucleotide repeat expansion and ALS patients with no mutations in known ALS-associated genes and we downregulated S100A4 using siRNA or the S100A4 transcriptional inhibitor niclosamide. Mice overexpressing human FUS were adopted to assess the effects of niclosamide in vivo on ALS pathology. Results We demonstrated that S100A4 underlies impaired autophagy and a profibrotic phenotype, which characterize ALS fibroblasts. Indeed, its inhibition reduces inflammatory, autophagic, and profibrotic pathways in ALS fibroblasts, and interferes with different markers known as pathogenic in the disease, such as mTOR, SQSTM1/p62, STAT3, α-SMA, and NF-κB. Importantly, niclosamide in vivo treatment of ALS-FUS mice reduces the expression of S100A4, α-SMA, and PDGFRβ in the spinal cord, as well as gliosis in central and peripheral nervous tissues, together with axonal impairment and displays beneficial effects on muscle atrophy, by promoting muscle regeneration and reducing fibrosis. Conclusion Our findings show that S100A4 has a role in ALS-related mechanisms, and that drugs such as niclosamide which are able to target inflammatory and fibrotic pathways could represent promising pharmacological tools for ALS.

scholarly journals The Biocompatibility of a New Erythritol-and Xyltol-Containing Fluoride Toothpaste

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 935
Author(s):  
Barbara Cvikl ◽  
Adrian Lussi
Keyword(s):  
Cell Types ◽  
Basic Function ◽  
Mouse Fibroblast ◽  
Fibroblast Cells ◽  
Lauryl Sulfate ◽  
Fluoride Release ◽  
Beneficial Effects ◽  
Biofilm Removal ◽  
The Mean ◽  
Different Cell Types

The basic function of toothpastes is biofilm removal in order to prevent caries and gingivitis. Toothpastes should provide maximal fluoride availability, optimal abrasivity, and ingredients that do not interfere with fluoride release but should have additional beneficial effects. Further, the effect on cells of the oral cavity is of the utmost importance. We investigated several biological parameters of a new toothpaste (AirFlow-AF) that contains fluoride, xylitol and erythritol but no sodium lauryl sulfate and compared them to commercially available toothpastes (Zendium-Ze, Sensodyne-Se, OdolMed-OM, OralB-OB). The half lethal concentration (LC50) as well as the proliferation behavior on gingival (GF), periodontal ligament (PDL), and mouse fibroblast cells (L929) were was tested. The mean LC50 values of AF on GF, PDL, and L929 were 16.2, 10.9, and 9.3, respectively. In comparison, the four other toothpastes showed mean LC50 values of 1.5 (OB), 1.2 (OM), 1.4 (Se), and 27.7 (Ze) on GF. Mean LC50 values on PDL and L929 were 1.0 and 0.2 (OB), 3.7 and 0.9 (OM), 1.2 and 0.6 (Se), and 25.4 and 5.6 (Ze), respectively. Proliferation behavior mainly confirmed the LC50 values. While cells after stimulation with AF returned to almost unimpaired proliferation behavior at 6%, cells were still strongly impaired after stimulation with all tested commercially toothpastes. AF showed high biocompatibility with different cell types.

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