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Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors.

ABSTRACT: PROBLEM:To study the mechanisms of placenta function and the role of extracellular vesicles (EVs) in pregnancy, it is necessary to develop an ex vivo system that retains placental cytoarchitecture and the primary metabolic aspects, in particular the release of EVs and soluble factors. Here, we developed such a system and investigated the pattern of secretion of cytokines, growth factors, and extracellular vesicles by placental villous and amnion tissues ex vivo. METHODS OF STUDY:Placental villous and amnion explants were cultured for 2 weeks at the air/liquid interface and their morphology and the released cytokines and EVs were analyzed. Cytokines were analyzed with multiplexed bead assays, and individual EVs were analyzed with recently developed techniques that involved EV capture with magnetic nanoparticles coupled to anti-EV antibodies and flow cytometry. RESULTS:Ex vivo tissues (i) remained viable and preserved their cytoarchitecture; (ii) maintained secretion of cytokines and growth factors; (iii) released EVs of syncytiotrophoblast and amnion epithelial cell origins that contain cytokines and growth factors. CONCLUSION:A system of ex vivo placental villous and amnion tissues can be used as an adequate model to study placenta metabolic activity in normal and complicated pregnancies, in particular to characterize EVs by their surface markers and by encapsulated proteins. Establishment and benchmarking the placenta ex vivo system may provide new insight in the functional status of this organ in various placental disorders, particularly regarding the release of EVs and cytokines. Such EVs may have a prognostic value for pregnancy complications.

SUBMITTER: Fitzgerald W

PROVIDER: S-EPMC6021205 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors.

Fitzgerald Wendy W Gomez-Lopez Nardhy N Erez Offer O Romero Roberto R Margolis Leonid L

American journal of reproductive immunology (New York, N.Y. : 1989) 20180504 1

<h4>Problem</h4>To study the mechanisms of placenta function and the role of extracellular vesicles (EVs) in pregnancy, it is necessary to develop an ex vivo system that retains placental cytoarchitecture and the primary metabolic aspects, in particular the release of EVs and soluble factors. Here, we developed such a system and investigated the pattern of secretion of cytokines, growth factors, and extracellular vesicles by placental villous and amnion tissues ex vivo.<h4>Methods of study</h4>P ...[more]

PMID: 29726582

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Project description:Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors, and functional microRNAs (miRNAs) that may modulate expression of recipient cell genes. As paracrine factors, neutrophil- and macrophage-derived EVs exert immunosuppressive and immune-stimulating effects on dendritic cells, respectively. Dendritic cell-derived EVs mediate alloantigen spreading and modulate antigen presentation to T lymphocytes. At systemic level, EVs exert pleiotropic effects on complement and coagulation. Depending on their biogenesis, they can amplify complement activation or shed complement inhibitors and prevent cell lysis. Likewise, endothelial- and platelet-derived EVs can exert procoagulant/prothrombotic effects and also promote endothelial survival and angiogenesis after ischemic injury. Kidney endothelial- and tubular-derived EVs play a key role in ischemia-reperfusion injury (IRI) and during the healing process; additionally, they can trigger rejection by inducing both alloimmune and autoimmune responses. Endothelial EVs have procoagulant/pro-inflammatory effects and can release sequestered self-antigens, generating a tissue-specific autoimmunity. Renal tubule-derived EVs shuttle pro-fibrotic mediators (TGF-? and miR-21) to interstitial fibroblasts and modulate neutrophil and T-lymphocyte influx. These processes can lead to peritubular capillary rarefaction and interstitial fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells (MSCs), have been employed as a therapeutic tool in experimental models of rejection and IRI. These particles protect tubular and endothelial cells (by inhibition of apoptosis and inflammation-fibrogenesis or by inducing autophagy) and stimulate tissue regeneration (by triggering angiogenesis, cell proliferation, and migration). Finally, urinary and serum EVs represent potential biomarkers for delayed graft function (DGF) and acute rejection. In conclusion, EVs sustain an intricate crosstalk between graft tissue and innate/adaptive immune systems. EVs play a major role in allorecognition, IRI, autoimmunity, and alloimmunity and are promising as biomarkers and therapeutic tools in KT.

Dataset Information

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors.

Publications

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors.

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