scholarly journals Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves

2019 ◽  
Author(s):  
Benedikt Kirchner ◽  
Dominik Buschmann ◽  
Vijay Paul ◽  
Michael W. Pfaffl
Keyword(s):  
Extracellular Vesicles ◽  
Expression Profiles ◽  
Bovine Milk ◽  
Cell Types ◽  
Specific Protein ◽  
In Vivo Experiments ◽  
Neonatal Calves ◽  
Almost All

Abstract Background Extracellular vesicles (EVs) such as exosomes are key regulators of intercellular communication that can be found in almost all bio fluids. Although studies in the last decade have made great headway in discerning the role of EVs in many physiological and pathophysiological processes, the bioavailability and impact of dietary EVs and their cargo still remain to be elucidated. Due to its widespread consumption and high content of EV-associated microRNAs and proteins, a major focus in this field has been set on EVs in bovine milk and colostrum. Despite promising in vitro studies in recent years that show high resiliency of milk EVs to degradation and uptake of milk EV cargo in a variety of intestinal and blood cell types, in vivo experiments continue to be inconclusive and sometimes outright contradictive. Results To resolve this discrepancy, we assessed the potential postprandial transfer of colostral EVs to the circulation of newborn calves by analysing colostrum-specific protein and miRNAs, including specific isoforms (isomiRs) in cells, EV isolations and unfractionated samples from blood and colostrum. Our findings reveal distinct populations of EVs in colostrum and blood from cows that can be clearly separated by density, particle concentration and protein content (BTN1A1, MFGE8). Postprandial blood samples of calves show a time-dependent increase in EVs that share morphological and protein characteristics of colostral EVs. Analysis of miRNA expression profiles by Next-Generation Sequencing gave a different picture however. Although significant postprandial expression changes could only be detected for calf EV samples, expression profiles show very limited overlap with highly expressed miRNAs in colostral EVs or colostrum in general. Conclusions Taken together our results indicate a selective uptake of membrane-associated protein cargo but not luminal miRNAs from colostral EVs into the circulation of neonatal calves.

scholarly journals Plant-Derived Extracellular Vesicles: Current Findings,Challenges, and Future Applications

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 411
Author(s):  
Nader Kameli ◽  
Anya Dragojlovic-Kerkache ◽  
Paul Savelkoul ◽  
Frank R. Stassen
Keyword(s):  
Human Health ◽  
Extracellular Vesicles ◽  
Preliminary Results ◽  
In Vivo Experiments ◽  
Health And Disease ◽  
Conducting Research ◽  
Protocol Standardization ◽  
Insight Into

In recent years, plant-derived extracellular vesicles (PDEVs) have gained the interest of many experts in fields such as microbiology and immunology, and research in this field has exponentially increased. These nano-sized particles have provided researchers with a number of interesting findings, making their application in human health and disease very promising. Both in vitro and in vivo experiments have shown that PDEVs can exhibit a multitude of effects, suggesting that these vesicles may have many potential future applications, including therapeutics and nano-delivery of compounds. While the preliminary results are promising, there are still some challenges to face, such as a lack of protocol standardization, as well as knowledge gaps that need to be filled. This review aims to discuss various aspects of PDEV knowledge, including their preliminary findings, challenges, and future uses, giving insight into the complexity of conducting research in this field.

scholarly journals Porcine Milk-Derived Small Extracellular Vesicles Promote Intestinal Immunoglobulin Production through pIgR

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1522
Author(s):  
Bin Zeng ◽  
Hailong Wang ◽  
Junyi Luo ◽  
Meiying Xie ◽  
Zhengjiang Zhao ◽  
...  
Keyword(s):  
Small Intestine ◽  
Extracellular Vesicles ◽  
Immunoglobulin A ◽  
Luciferase Reporter ◽  
Epithelial Cell Line ◽  
Intestinal Immunity ◽  
In Vivo Experiments ◽  
Porcine Milk

Secretory immunoglobulin A (SIgA) plays an important role in gut acquired immunity and mucosal homeostasis. Breast milk is the irreplaceable nutritional source for mammals after birth. Current studies have shown the potential functional role of milk-derived small extracellular vesicles (sEVs) and their RNAs cargo in intestinal health and immune regulation. However, there is a lack of studies to demonstrate how milk-derived sEVs affect intestinal immunity in recipient. In this study, through in vivo experiments, we found that porcine milk small extracellular vesicles (PM-sEVs) promoted intestinal SIgA levels, and increased the expression levels of polymeric immunoglobulin receptor (pIgR) both in mice and piglet. We examined the mechanism of how PM-sEVs increased the expression level of pIgR in vitro by using a porcine small intestine epithelial cell line (IPEC-J2). Through bioinformatics analysis, dual-luciferase reporter assays, and overexpression or knockdown of the corresponding non-coding RNAs, we identified circ-XPO4 in PM-sEVs as a crucial circRNA, which leads to the expression of pIgR via the suppression of miR-221-5p in intestinal cells. Importantly, we also observed that oral administration of PM-sEVs increased the level of circ-XPO4 and decreased the level of miR-221-5p in small intestine of piglets, indicating that circRNAs in milk-derived sEVs act as sponge for miRNAs in recipients. This study, for the first time, reveals that PM-sEVs have a capacity to stimulate intestinal SIgA production by delivering circRNAs to receptors and sponging the recipient’s original miRNAs, and also provides valuable data for insight into the role and mechanism of animal milk sEVs in intestinal immunity.

Exosomes derived from mmu_circ_0000623-modified ADSCs prevent liver fibrosis via activating autophagy

2020 ◽  
Vol 39 (12) ◽  
pp. 1619-1627 ◽  
Author(s):  
M Zhu ◽  
X Liu ◽  
W Li ◽  
L Wang
Keyword(s):  
Liver Fibrosis ◽  
Expression Profiles ◽  
Parenchymal Cell ◽  
Hepatic Tissue ◽  
Circular Rnas ◽  
In Vivo Experiments ◽  
Matrix Accumulation ◽  
Inhibitor Treatment

Prolonged parenchymal cell death leads to activation of fibrogenic cells, extracellular matrix accumulation, and eventually liver fibrosis. Increasing evidence shows that exosomes (Exos) secreted by adipose-derived mesenchymal stem cells (ADSCs) can be used to deliver circular RNAs (circRNAs) to treat liver fibrosis. To explore the uses of circRNA, circRNA expression profiles of hepatic tissue from normal and CCl4-induced mice were analyzed using high-throughput circRNA microarrays. The result showed that mmu_circ_0000623 expression was downregulated in CCl4-induced mice. Bioinformatics analysis and luciferin reporter experiments showed that mmu_circ_0000623 interacted with and regulated miR-125/ATG4D. In vitro and in vivo experiments showed that Exos from ADSCs, especially from mmu_circ_0000623-modified ADSCs, significantly suppressed CCl4-induced liver fibrosis by promoting autophagy activation. Autophagy inhibitor treatment significantly reversed the treatment effects of Exos. Proteins involved in autophagy and autophagy plaques positive for ATG4D expression were regulated by mmu_circ_0000623/miR-125. Our study found that Exos derived from mmu_circ_0000623-modified ADSCs prevented liver fibrosis via activating autophagy.

scholarly journals Propofol impairs specification of retinal cell types in zebrafish by inhibiting Zisp-mediated Noggin-1 palmitoylation and trafficking

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Lizhu Hu ◽  
Delong Wang ◽  
Ruiting Wang ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Cell Formation ◽  
Cognitive Disorders ◽  
Cell Types ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Retinal Cell ◽  
Soluble Form ◽  
In Vivo Experiments

Abstract Background Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. Here, we aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway. Methods The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, whole-mount in situ hybridization and immunohistochemistry, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, 5-ethynyl-2′-deoxyuridine labeling, co-immunoprecipitation, and acyl–biotin exchange labeling were used to identify the potential mechanisms of propofol-mediated zisp expression and determine its effect on the specification of retinal cell types. Results Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through the inhibition of Zisp expression. Furthermore, Zisp promoted the stabilization and secretion of a soluble form of the membrane-associated protein Noggin-1, a specific palmitoylation substrate. Conclusions Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.

Propofol Impairs Specification of Retinal Cell Types in Zebrafish by Inhibiting Zisp-mediated Noggin-1 Palmitoylation and Trafficking

2020 ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Lizhu Hu ◽  
Delong Wang ◽  
Ruiting Wang ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Cell Formation ◽  
Cognitive Disorders ◽  
Cell Types ◽  
Retinal Cell ◽  
Soluble Form ◽  
In Vivo Experiments ◽  
Developing Neurons

Abstract Background: Propofol can have adverse effects on developing neurons, leading to cognitive disorders. However, the mechanism remains elusive. Here, we aimed to investigate the effect and molecular mechanism of propofol on neuronal development in zebrafish. Methods: The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, Whole-mount in situ hybridization and immunohistochemistry, quantitative real-time PCR, TUNEL, EdU, Co-Immunoprecipitation and acyl–biotin exchange (ABE) labeling method were carried out to demonstrate the potential mechanisms of propofol-mediated zisp expression and specification of retinal cell types.Results: Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through inhibition of Zisp expression. Furthermore, Zisp promoted the secretion of a soluble form and the stabilization of a membrane-associated form of Noggin-1, a specific palmitoylation substrate.Conclusions: Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.

scholarly journals Renal Regenerative Potential of Extracellular Vesicles Derived from miRNA-Engineered Mesenchymal Stromal Cells

2019 ◽  
Vol 20 (10) ◽  
pp. 2381 ◽  
Author(s):  
Marta Tapparo ◽  
Stefania Bruno ◽  
Federica Collino ◽  
Gabriele Togliatto ◽  
Maria Chiara Deregibus ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Interventions ◽  
In Vivo Models ◽  
Regenerative Effect ◽  
In Vivo Experiments ◽  
Renal Regeneration

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled molecules, miRNAs have a relevant role in the pro-regenerative effects of EVs and are a promising target for therapeutic interventions. The aim of this study was to increase the content of specific miRNAs in EVs that are known to be involved in the pro-regenerative effect of EVs, and to assess the capacity of modified EVs to contribute to renal regeneration in in vivo models with acute kidney injuries. To this purpose, MSCs were transiently transfected with specific miRNA mimics by electroporation. Molecular analyses showed that, after transfection, MSCs and derived EVs were efficiently enriched in the selected miRNAs. In vitro and in vivo experiments indicated that EVs engineered with miRNAs maintained their pro-regenerative effects. Of relevance, engineered EVs were more effective than EVs derived from naïve MSCs when used at suboptimal doses. This suggests the potential use of a low amount of EVs (82.5 × 106) to obtain the renal regenerative effect.

scholarly journals Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1596
Author(s):  
David R. Brigstock
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Chronic Injury ◽  
Increased Risk ◽  
End Stage ◽  
Parenchymal Cells ◽  
Risk Of Cancer ◽  
Organ Fibrosis

Fibrosis is the unrelenting deposition of excessively large amounts of insoluble interstitial collagen due to profound matrigenic activities of wound-associated myofibroblasts during chronic injury in diverse tissues and organs. It is a highly debilitating pathology that affects millions of people globally and leads to decreased function of vital organs and increased risk of cancer and end-stage organ disease. Extracellular vesicles (EVs) produced within the chronic wound environment have emerged as important vehicles for conveying pro-fibrotic signals between many of the cell types involved in driving the fibrotic response. On the other hand, EVs from sources such as stem cells, uninjured parenchymal cells, and circulation have in vitro and in vivo anti-fibrotic activities that have provided novel and much-needed therapeutic options. Finally, EVs in body fluids of fibrotic individuals contain cargo components that may have utility as fibrosis biomarkers, which could circumvent current obstacles to fibrosis measurement in the clinic, allowing fibrosis stage, progression, or regression to be determined in a manner that is accurate, safe, minimally-invasive, and conducive to repetitive testing. This review highlights the rapid and recent progress in our understanding of EV-mediated fibrotic pathogenesis, anti-fibrotic therapy, and fibrosis staging in the lung, kidney, heart, liver, pancreas, and skin.

scholarly journals Biodistribution, Uptake and Effects Caused by Cancer-Derived Extracellular Vesicles

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Lilite Sadovska ◽  
Cristina Bajo Santos ◽  
Zane Kalniņa ◽  
Aija Linē
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Cell Phenotype ◽  
Chromosomal Dna ◽  
Metastatic Niche ◽  
Paracrine Signalling ◽  
Cancerous Cell ◽  
The Impact

Extracellular vesicles (EVs) have recently emerged as important mediators of intercellular communication. They are released in the extracellular space by a variety of normal and cancerous cell types and have been found in all human body fluids. Cancer-derived EVs have been shown to carry lipids, proteins, mRNAs, non-coding and structural RNAs and even extra-chromosomal DNA, which can be taken up by recipient cells and trigger diverse physiological and pathological responses. An increasing body of evidence suggests that cancer-derived EVs mediate paracrine signalling between cancer cells. This leads to the increased invasiveness, proliferation rate and chemoresistance, as well as the acquisition of the cancer stem cell phenotype. This stimulates angiogenesis and the reprogramming of normal stromal cells into cancer-promoting cell types. Furthermore, cancer-derived EVs contribute to the formation of the pre-metastatic niche and modulation of anti-tumour immune response. However, as most of these data are obtained by in vitro studies, it is not entirely clear which of these effects are recapitulated in vivo. In the current review, we summarize studies that assess the tissue distribution, trafficking, clearance and uptake of cancer-derived EVs in vivo and discuss the impact they have, both locally and systemically.

scholarly journals Progress and Future Challenges of Human Induced Pluripotents Stem Cell in Regenerative Medicine

2011 ◽  
Vol 3 (2) ◽  
pp. 76
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Stem Cells ◽  
Somatic Cell ◽  
Expression Profiles ◽  
Human Fibroblasts ◽  
Embryonic Stem ◽  
Cell Types ◽  
Differentiation Potential ◽  
Human Ipscs

BACKGROUND: Less than a decade ago the prospect for reprogramming the human somatic cell looked bleak at best. It seemed that the only methods at our disposal for the generation of human isogenic pluripotent cells would have to involve somatic cell nuclear transfer (SCNT). Shinya Yamanaka in August 2006 in his publication (Cell) promised to change everything by showing that it was apparently very simple to revert the phenotype of a differentiated cell to a pluripotent one by overexpressing four transcription factors in murine fibroblasts.CONTENT: Mouse and human somatic cells can be genetically reprogrammed into induced pluripotent stem cells (iPSCs) by the expression of a defined set of factors (Oct4, Sox2, c-Myc, and Klf4, as well as Nanog and LIN28). iPSCs could be generated from mouse and human fibroblasts as well as from mouse liver, stomach, pancreatic, neural stem cells, and keratinocytes. Similarity of iPSCs and embryonic stem cells (ESCs) has been demonstrated in their morphology, global expression profiles, epigenetic status, as well as in vitro and in vivo differentiation potential for both mouse and human cells. Many techniques for human iPSCs (hiPSCs) derivation have been developed in recent years, utilizing different starting cell types, vector delivery systems, and culture conditions. A refined or perfected combination of these techniques might prove to be the key to generating clinically applicable hiPSCs.SUMMARY: iPSCs are a revolutionary tool for generating in vitro models of human diseases and may help us to understand the molecular basis of epigenetic reprogramming. Progress of the last four years has been truly amazing, almost verging on science fiction, but if we can learn to produce such cells cheaply and easily, and control their differentiation, our efforts to understand and fight disease will become more accessible, controllable and tailored. Ability to safely and efficiently derive hiPSCs may be of decisive importance to the future of regenerative medicine.KEYWORDS: iPSCs, ESC, reprogramming factor, reprogramming efficiency, somatic cell

scholarly journals Stem cells: an origin and marks

2020 ◽  
Vol 22 (2) ◽  
pp. 211-216
Author(s):  
A. V. Moskalev ◽  
B. Y. Gumilevskiy ◽  
A. V. Apchel ◽  
V. N. Cygan
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Molecular Marker ◽  
Population Level ◽  
Cell Types ◽  
Stem Cell Marker ◽  
Wide Range ◽  
Almost All

The basic physiological functions of stem cells are given: the ability to reproduce and generate offspring, which are manifested at the level of the population, and not of a single cell. The manifestation of these functions depends on the quantitative and qualitative composition of the microenvironment. Stem cells consist of two fundamentally different types: pluripotent, which exist only in vitro (in vitro) and tissue, existing in the postpartum body (in vivo). Stem cells can be replaced without limitation in vitro and lead to the appearance of a wide range of cell types. Tissue stem cells under normal conditions do not generate cells characteristic of other types of tissue. Stem cells include cells capable of expressing the gene products characteristic of them. However, there is no universal marker to differentiate stem cells from non-stem cells. A key marker of pluripotency is the transcription factor - a pituitary-specific transcription factor is positive. A component that can be found in almost all types of stem cells is the telomerase complex. Another stem cell marker is called CD34 glycoprotein. The functional activity of stem cells is associated with a molecular marker referred to as leucine-rich repeat containing G-protein bound to receptor 5. However, other types of cells do not express this marker. The physiological capabilities of stem cells depend both on the cells themselves and on their environment. The most reliable way to identify stem cells is to determine their phenotype in vivo. This suggests that stem cells do not carry a universal molecular marker. Most likely, they have significant differences from transplanted cells, and these differences cannot always be detected in individual cells, but only at the population level.

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