News

Aug 23, 2016

Join the SELECTBIO Extracellular Vesicles Virtual Event made available from September 21st, and hear leading researchers talk about topics within EV biology and therapeutic potential!

 

Information

General information, events and/or links.

 

 

EV literature (RSS feed from PubMed)

Search terms: exosomes OR "extracellular vesicles" OR microvesicles OR microparticles. Direct link to the PubMed search here.

Thermoresponsive Gel Embedding Adipose Stem Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery Strategy.

-

Related Articles

Thermoresponsive Gel Embedding Adipose Stem Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery Strategy.

ACS Nano. 2018 Sep 19;:

Authors: A Silva AK, Perretta S, Perrod G, Pidial L, Lindner V, Carn F, Lemieux S, Alloyeau D, Boucenna I, Menasché P, Dallemagne B, Gazeau F, Wilhelm C, Cellier C, Clément O, Rahmi G

Abstract
Extracellular vesicles (EVs) are increasingly envisioned to be the next-generation of biological proregenerative nanotherapeutic agents, as already demonstrated for heart, kidney, liver, lung injury, brain and skin regeneration. Herein, we explore another potential EV therapeutic application, for fistula healing, together with a local minimally-invasive delivery strategy. Allogenic extracellular vesicles (EVs) from adipose tissue-derived stromal cells (ADSCs) are administered in a porcine fistula model through a thermoresponsive pluronic F-127 (PF-127) gel, injected locally at 4°C and gelling at body temperature to retain EVs in the entire fistula tract. Complete fistula healing is reported to be 100% for the gel + EVs group, 67% for the gel group and 0% for the control, supporting a therapeutic use of Pluronic F-127 gel alone or combined with EVs. However, only the combination of gel and EVs results in a statistically significant (i) reduction of fibrosis, (ii) decline of inflammatory response, (iii) decrease in the density of myofibroblasts and (iv) increase of angiogenesis. Overall, we demonstrate that ADSC-EV delivery into a PF-127 gel represents a successful local minimally-invasive strategy to induce a therapeutic effect in a swine fistula model. Our study brings prospects in EV administration strategies and in the management of postoperative fistulas.

PMID: 30231208 [PubMed - as supplied by publisher]

Enhanced Skull Bone Regeneration by Sustained Release of BMP-2 in Interpenetrating Composite Hydrogels.

-

Related Articles

Enhanced Skull Bone Regeneration by Sustained Release of BMP-2 in Interpenetrating Composite Hydrogels.

Biomacromolecules. 2018 Sep 19;:

Authors: Kim S, Kim J, Mani G, Yoon M, Hwang MP, Wang Y, Kang BJ, Kim K

Abstract
Direct administration of bone morphogenetic protein-2 (BMP-2) for bone regeneration could cause various clinical side effects such as osteoclast activation, inflammation, adipogenesis, and bone cyst formation. In this study, thiolated gelatin/poly(ethylene glycol) diacrylate (PEGDA) interpenetrating (IPN) composite hydrogels were developed for guided skull bone regeneration. To promote bone regeneration, either polycation-based coacervates (Coa) or gelatin microparticles (GMPs) were incorporated within IPN gels as BMP-2 carriers. Both BMP-2 loaded Coa and BMP-2 loaded GMPs showed significantly enhanced in-vitro alkaline phosphate (ALP) activity of human mesenchymal stem cells (hMSCs) than non-BMP-2 treated control. Moreover, BMP-2 loaded GMPs group exhibited statistically increased ALP activity than both bolus BMP-2 administration and BMP-2 loaded Coa group, indicating that our carriers could protect and maintain biological activity of cargo BMP-2. Sustained release kinetics of BMP-2 from IPN composite hydrogels could be controlled by different formulations. For in-vivo bone regeneration, various IPN gel formulations (i.e., (1) control, (2) only hydrogel, (3) hydrogel with bolus BMP-2, (4) hydrogel with BMP-2-loaded Coa, and (5) hydrogel with BMP-2-loaded GMPs) were bilaterally implanted into 5 mm-sized rat calvarial defects. After 4 weeks, micro-CT and histological analysis were performed to evaluate new bone formation. Significantly higher scores for bony bridging and union were observed in BMP-2-loaded Coa and BMP-2-loaded GMP groups as compared to other formulations. In addition, rats treated with BMP-2-loaded GMPs showed a significantly higher ratio of bone volume/total volume and lower trabecular separation scores than others. Finally, rats treated with either Coa or GMP groups exhibited a significant increase in bone formation area, as assessed via histomorphometric analysis Taken together, it could be concluded that Coa and GMPs were effective carriers to maintain the bioactivity of cargo BMP-2 during its sustained release. Consequently, our IPN composite hydrogel system that combines such BMP-2 carriers could effectively promote skull bone regeneration.

PMID: 30231204 [PubMed - as supplied by publisher]

Role of p53 and transcription-independent p53-induced apoptosis in shear-stimulated megakaryocytic maturation, particle generation, and platelet biogenesis.

-

Related Articles

Role of p53 and transcription-independent p53-induced apoptosis in shear-stimulated megakaryocytic maturation, particle generation, and platelet biogenesis.

PLoS One. 2018;13(9):e0203991

Authors: Luff SA, Kao CY, Papoutsakis ET

Abstract
Megakaryocytes (Mks) derive from hematopoietic stem and progenitor cells (HSPCs) in the bone marrow and develop into large, polyploid cells that eventually give rise to platelets. As Mks mature, they migrate from the bone marrow niche into the vasculature, where they are exposed to shear forces from blood flow, releasing Mk particles (platelet-like particles (PLPs), pro/preplatelets (PPTs), and Mk microparticles (MkMPs)) into circulation. We have previously shown that transcription factor p53 is important in Mk maturation, and that physiological levels of shear promote Mk particle generation and platelet biogenesis. Here we examine the role of p53 in the Mk shear-stress response. We show that p53 is acetylated in response to shear in both immature and mature Mks, and that decreased expression of deacetylase HDAC1, and increased expression of the acetyltransferases p300 and PCAF might be responsible for these changes. We also examined the hypothesis that p53 might be involved in the shear-induced Caspase 3 activation, phosphatidylserine (PS) externalization, and increased biogenesis of PLPs, PPTs, and MkMPs. We show that p53 is involved in all these shear-induced processes. We show that in response to shear, acetyl-p53 binds Bax, cytochrome c is released from mitochondria, and Caspase 9 is activated. We also show that shear-stimulated Caspase 9 activation and Mk particle biogenesis depend on transcription-independent p53-induced apoptosis (TIPA), but PS externalization is not. This is the first report to show that shear flow stimulates TIPA and that Caspase 9 activation and Mk-particle biogenesis are directly modulated by TIPA.

PMID: 30231080 [PubMed - in process]

Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis.

-

Related Articles

Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis.

PLoS One. 2018;13(9):e0202590

Authors: Laso-García F, Ramos-Cejudo J, Carrillo-Salinas FJ, Otero-Ortega L, Feliú A, Gómez-de Frutos M, Mecha M, Díez-Tejedor E, Guaza C, Gutiérrez-Fernández M

Abstract
Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and as possible therapeutic agents in inflammation-mediated demyelinating diseases, including multiple sclerosis (MS). In the present study, we investigated whether intravenously administered EVs derived from mesenchymal stem cells (MSCs) from human adipose tissue might mediate recovery in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, a progressive model of MS. SJL/J mice were subjected to EV treatment once the disease was established. We found that intravenous EV administration improved motor deficits, reduced brain atrophy, increased cell proliferation in the subventricular zone and decreased inflammatory infiltrates in the spinal cord in mice infected with TMEV. EV treatment was also capable of modulating neuroinflammation, given glial fibrillary acidic protein and Iba-1 staining were reduced in the brain, whereas myelin protein expression was increased. Changes in the morphology of microglial cells in the spinal cord suggest that EVs also modulate the activation state of microglia. The clear reduction in plasma cytokine levels, mainly in the Th1 and Th17 phenotypes, in TMEV mice treated with EVs confirms the immunomodulatory ability of intravenous EVs. According to our results, EV administration attenuates motor deficits through immunomodulatory actions, diminishing brain atrophy and promoting remyelination. Further studies are necessary to establish EV delivery as a possible therapy for the neurodegenerative phase of MS.

PMID: 30231069 [PubMed - in process]

Intercellular Communication between Airway Epithelial Cells is Mediated by Exosome-Like Vesicles.

-

Related Articles

Intercellular Communication between Airway Epithelial Cells is Mediated by Exosome-Like Vesicles.

Am J Respir Cell Mol Biol. 2018 Sep 19;:

Authors: Gupta R, Radicioni G, Abdelwahab S, Dang H, Carpenter J, Chua M, Mieczkowski PA, Sheridan J, Randell SH, Kesimer M

Abstract
Airway epithelium structure/function can be altered by local inflammatory/immune signals, and this process is called epithelial remodeling. The mechanism by which this innate response is regulated, which causes mucin/mucus overproduction, is largely unknown. Exosomes are nano-vesicles that can be secreted and internalized by cells to transport cellular cargo, such as proteins, lipids, and miRNA. The objective of this study was to understand the role exosomes play in airway remodeling through cell-cell communication. We utilized two different human airway cell cultures: primary tracheobronchial (HTBE) cells and a cultured airway epithelial cell line (Calu-3). After intercellular exosomal transfer, comprehensive proteomic and genomic characterization of cell secretions and exosomes was performed. Quantitative proteomics and exosomal miRNA analysis profiles indicated that the two cell types are fundamentally distinct. HTBE cell secretions were typically dominated by fundamental innate/protective proteins, including mucin MUC5B, and Calu-3 cell secretions were dominated by pathology-associated proteins, including mucin MUC5AC. After exosomal transfer/intake, approximately 20% of proteins, including MUC5AC and MUC5B, were significantly altered in HTBE secretions. After exosome transfer, approximately 90 miRNAs (~4%) were upregulated in HTBE exosomes, whereas Calu-3 exosomes exhibited a preserved miRNA profile. Together, our data suggest that the transfer of exosomal cargo between airway epithelial cells significantly alters the qualitative and quantitative profiles of airway secretions, including mucin hypersecretion, and the miRNA cargo of exosomes in target cells. This finding indicates that cellular information can be carried between airway epithelial cells via exosomes, which may play an important role in airway biology and epithelial remodeling.

PMID: 30230353 [PubMed - as supplied by publisher]

Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune competence.

-

Related Articles

Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune competence.

Clin Exp Immunol. 2018 Sep 19;:

Authors: Theodoraki MN, Hoffmann TK, Jackson EK, Whiteside TL

Abstract
Exosomes in plasma of head and neck squamous cell carcinoma (HNSCC) patients comprise subsets of vesicles derived from various cells. Recently, we separated CD3(+) from CD3(-) exosomes by immune capture. CD3(-) exosomes were largely tumour-derived (CD44v3+ ). Both subsets carried immunosuppressive proteins and inhibited functions of human immune cells. The role of these subsets in immune cell reprogramming by the tumour was investigated by focusing on the adenosine pathway components. Spontaneous adenosine production by CD3(+) or CD3(-) exosomes was measured by mass spectrometry, as was the production of adenosine by CD4+ CD39+ regulatory T cells (Treg ) co-incubated with these exosomes. The highest level of CD39/CD73 ectoenzymes and of adenosine production was found in CD3(-) exosomes in patients with the stages III/IV HNSCCs). Also, the production of 5'-AMP and purines was significantly higher in Treg co-incubated with CD3(-) than CD3(+) exosomes. Consistently, CD26 and adenosine deaminase (ADA) levels were higher in CD3(+) than CD3(-) exosomes. ADA and CD26 levels in CD3(+) exosomes were significantly higher in patients with early (stages I/II) than advanced (stages III/IV) disease. HNSCC patients receiving and responding to photodynamic therapy had increased ADA levels in CD3(+) exosomes with no increase in CD3(-) exosomes. The opposite roles of CD3(+) ADA+ CD26+ and CD3(-) CD44v3+ adenosine-producing exosomes in early versus advanced HNSCC suggest that, like their parent cells, these exosomes serve as surrogates of immune suppression in cancer.

PMID: 30229863 [PubMed - as supplied by publisher]

Tax-mRNA-carrying exosomes from HTLV-1-infected cells can induce IFN-γ production in vitro.

-

Related Articles

Tax-mRNA-carrying exosomes from HTLV-1-infected cells can induce IFN-γ production in vitro.

AIDS Res Hum Retroviruses. 2018 Sep 19;:

Authors: Otaguiri KK, Dos Santos DF, Slavov SN, Depieri L, Palma PVB, Meirelles FV, Covas DT, Da Silveira JC, Kashima S

Abstract
BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). The development of HAM/TSP, a chronic neuroinflammatory disease, is correlated to complex interaction between the host immune response and the infecting virus. Tax expression plays important role in HAM/TSP pathogenesis by activating various cellular genes, including the cytokines IFN-γ and TNF-α. Exosomes have emerged as an important factor of cell-to-cell communication contributing to diverse cellular processes, including immune modulation. Considering the potential role of exosomes in modulating the immune response and inflammation, the main objective of this study was to examine if HTLV-1-infected cells produce exosomes carrying viral proteins or inflammatory molecules, which can participate in the chronic inflammation which is observed in patients with HAM/TSP.
METHODS: Exosomes were isolated from HTLV-1-infected cell line, evaluated for the tax mRNA presence and tested for the ability to activate peripheral mononuclear cells (PBMC) in inducing an inflammatory immune response.
RESULTS: We observed that the proinflammatory cytokines, IFN-γ and TNF-α, were upregulated in T-cells after treatment of the PBMC with Tax carrying exosomes compared to the negative control. IL-4, Granzyme B and Perforin did not show alterations.
CONCLUSION: Taken together, these results suggest that exosomes carrying Tax isolated from HTLV-1-infected cells might induce the production of proinflammatory cytokines and activate T helper (Th)1, and not Th2-immune response. If this finding is further confirmed, this study may have impact on investigations on the pathogenesis of HAM-TSP and the inflammatory response involved in this disease.

PMID: 30229663 [PubMed - as supplied by publisher]

Direct observation of dynamic interaction between a functional group in a single SBR chain and an inorganic matter surface.

-

Related Articles

Direct observation of dynamic interaction between a functional group in a single SBR chain and an inorganic matter surface.

Sci Rep. 2018 Sep 18;8(1):13982

Authors: Shinohara KI, Makida Y

Abstract
As a composite of hybrid organic-inorganic materials, blending hydrophilic silica microparticles with oil-extended rubber can improve vehicle tire performance but the nanometer scale effects of microparticle inclusion have not been thoroughly studied. Here, we used atomic force microscopy (AFM) video imaging to closely investigate the behavior of functionalized and unmodified styrene-butadiene rubber (SBR), as models for tire rubber, on mica surfaces. The hydrophilic silica microparticle surface could be simulated by a mica substrate because both have silanol groups on their surface. Using AFM video imaging, we tracked the behavior of individual SBR polymer chains on mica surfaces to reveal how polymer modification affects the interaction of SBR with mica surfaces. We measured the diffusion coefficients and spring constants of single SBR polymer chains for the first time, demonstrating that it is possible to parameterize the relationship between the molecular dynamic structure of a polymer and rubber properties of the vulcanized compound.

PMID: 30228343 [PubMed - in process]

Prognostic role of circulating exosomal miR-425-3p for the response of NSCLC to platinum-based chemotherapy.

-

Related Articles

Prognostic role of circulating exosomal miR-425-3p for the response of NSCLC to platinum-based chemotherapy.

Cancer Epidemiol Biomarkers Prev. 2018 Sep 18;:

Authors: Yuwen D, Ma Y, Wang D, Gao J, Li X, Xue W, Fan M, Xu Q, Shen Y, Shu Y

Abstract
BACKGROUND: Platinum-based doublets with a third-generation agent are the recommended option for many NSCLC patients with no contraindications to platinum compounds. Unfortunately, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance.
METHODS: Circulating exosomal miRNAs were isolated and used to perform HiSeq deep sequencing analyses on serum pool samples from platinum-resistant or platinum-sensitive patients, and six exosomal miRNAs were further validated for their predictive utility by RT-qPCR in 170 serum samples of advanced NSCLC patients. Gain- and loss-of-function experiments clarified the responsiveness-regulating role of the clinically relevant miRNA. Immunohistochemical analyses were performed to evaluate the association between basal autophagy in lung cancer tissues and responsiveness in 203 NSCLC patients receiving platinum-based chemotherapy.
RESULTS: Six circulating exosomal miRNAs (miR-425-3p, miR-1273h, miR-4755-5p, miR-9-5p, miR-146a-5p, and miR-215-5p) were found to be differentially expressed with the largest fold change in platinum-resistant patients compared to platinum-sensitive patients. High miR-425-3p proved to be a potent predictive biomarker for low responsiveness and poor PFS. Mechanistically, miR-425-3p up-regulated the autophagic levels via targeting AKT1, leading to the decrease in therapeutic response. Concordantly, high levels of basal autophagy in lung cancer tissues correlate with low responsiveness in NSCLC patients within the early and advanced disease stages.
CONCLUSIONS: Our study highlights circulating exosomal miR-425-3p as a potential biomarker for improved predictions of the clinical response to platinum-based chemotherapy in NSCLC patients.
IMPACT: This study provides the first evidence that miR-425-3p in NSCLC patients-derived exosomes can be a marker for predicating the clinical response to platinum-based chemotherapy.

PMID: 30228154 [PubMed - as supplied by publisher]

Changes in the biochemical taste of cytoplasmic and cell-free DNA are major fuels for inflamm-aging.

-

Related Articles

Changes in the biochemical taste of cytoplasmic and cell-free DNA are major fuels for inflamm-aging.

Semin Immunol. 2018 Sep 15;:

Authors: Storci G, De Carolis S, Olivieri F, Bonafè M

Abstract
Inflamm-aging depicts the progressive activation of the innate immune system that accompanies human aging. Its role as a disease-predisposing condition has been proposed, but its molecular basis is still poorly understood. A wealth of literature conveys that, particularly upon stress, nuclear and mitochondrial genomes are released into the cytoplasmic and extracellular compartments. Cytoplasmic (cy) and cell-free (cf) DNA pools trigger inflammation and innate immunity at local and systemic level. In particular, cyDNA plays a crucial role in the phenomenon of cell senescence and in the cognate pro-inflammatory secretome. Here we propose that changes in a variety of biochemical characteristics "tastes" of cy- and cf-DNA (e.g. the amount of 8-oxo-deoxy-guanosine and 5-methyl-deoxy-cytosine, the proportion of DNA hybridized with RNA) potentially affect the capability of these DNA pools to ignite the innate immune system. We also underpin that telomeric sequences are major components of the cy/cfDNA payload. Telomere shortening, a hallmark of aging, causes the depletion of telomeric sequences in cy/cfDNA pool, thus unleashing their potential to exert an age-related activation of the innate immune system. Finally, we posit that various sources of DNA (extracellular vesicles, the commensal metagenome and food) contribute to the cy/cfDNA payloads. We speculate that changes in the biochemical "taste" of cy/cfDNA are major modifiers of inflamm-aging.

PMID: 30227944 [PubMed - as supplied by publisher]

Sinomenine Protects Against Morphine Dependence through the NMDAR1/CAMKII/CREB Pathway: A Possible Role of Astrocyte-Derived Exosomes.

-

Related Articles

Sinomenine Protects Against Morphine Dependence through the NMDAR1/CAMKII/CREB Pathway: A Possible Role of Astrocyte-Derived Exosomes.

Molecules. 2018 Sep 17;23(9):

Authors: Ou J, Zhou Y, Li C, Chen Z, Li H, Fang M, Zhu C, Huo C, Yung KK, Li J, Luo C, Mo Z

Abstract
Sinomenine is a nonaddictive alkaloid used to prevent morphine dependence, even thoughits mechanism isnot fully understood. Astrocytes aggravate the pathological process in their neighboring cellsthrough exosomes in central nervous system diseases. However, the effect of sinomenine on astrocyte-derived exosomes for the amelioration of morphine dependence has not been reported yet. In this study, we found that sinomenine prevented the morphine-induced conditionedplace preference in mice. Sinomenine reduced the levels of cAMP and intracellular Ca2+ in morphine-treated SH-SY5Y cells. Moreover, sinomenine inhibited the expressions of p-NMDAR1/NMDAR1, p-CAMKII/CAMKII, and p-CREB/CREB in the hippocampusof morphine-dependent mice and SH-SY5Y cells. Furthermore, we found that sinomenine inhibitedthe morphine-induced activation of astrocytesin vivo and in vitro. Afterwards, exosomes were isolated from cultured primary astrocytes treated with phosphate buffer saline (PBS, ctl-exo), morphine (mor-exo), or morphine and sinomenine (Sino-exo). Subsequently, morphine-treated SH-SY5Y cells were treated with ctl-exo, mor-exo, and Sino-exo. Results showed that Sino-exo reduced the level of cAMP, intracellular Ca2+, and the expression of p-CAMKII/CAMKII and p-CREB/CREB in morphine-treated SH-SY5Y cells. In conclusion, we demonstrated that sinomenine exhibited protective effects against morphine dependencein vivo and in vitro through theNMDAR1/CAMKII/CREB pathway. Sinomenine-induced alterationof the function of astrocyte-derived exosomes may contribute to the antidependence effects of sinomenine in morphine dependence.

PMID: 30227624 [PubMed - in process]

 

Previous page: Relevant links  Next page: EVents