P.111: Alpha and Beta Cell Crosstalk via Extracellular Vesicles

Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier—or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.

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Isolation, Characterization and Potential Role in Beta Cell-Endothelium Cross-Talk of Extracellular Vesicles Released from Human Pancreatic Islets

PLoS ONE ◽

10.1371/journal.pone.0102521 ◽

2014 ◽

Vol 9 (7) ◽

pp. e102521 ◽

Cited By ~ 53

Author(s):

Federico Figliolini ◽

Vincenzo Cantaluppi ◽

Michela De Lena ◽

Silvia Beltramo ◽

Renato Romagnoli ◽

...

Keyword(s):

Beta Cell ◽

Pancreatic Islets ◽

Extracellular Vesicles ◽

Cross Talk ◽

Potential Role ◽

Human Pancreatic Islets

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Extracellular vesicles in bone cell crosstalk

Nature Reviews Rheumatology ◽

10.1038/nrrheum.2017.191 ◽

2017 ◽

Vol 14 (1) ◽

pp. 2-3 ◽

Cited By ~ 2

Author(s):

Joanna Collison

Keyword(s):

Extracellular Vesicles ◽

Bone Cell ◽

Cell Crosstalk

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2102-P: Regulation of Alpha-Cell Function by Beta-Cell Extracellular Vesicles

Diabetes ◽

10.2337/db20-2102-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 2102-P

Author(s):

JAGAN KALIVARATHAN ◽

PRATHAB BALAJI SARAVANAN ◽

MARLON F. LEVY ◽

MAZHAR A. KANAK

Keyword(s):

Beta Cell ◽

Extracellular Vesicles ◽

Cell Function ◽

Alpha Cell ◽

Alpha Cell Function

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Extracellular Vesicles Released by Enterovirus-Infected EndoC-βH1 Cells Mediate Non-Lytic Viral Spread

Microorganisms ◽

10.3390/microorganisms8111753 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1753

Author(s):

Eitan Netanyah ◽

Matteo Calafatti ◽

Jeanette Arvastsson ◽

Eduardo Cabrera-Rode ◽

Corrado M. Cilio ◽

...

Keyword(s):

Beta Cell ◽

Beta Cells ◽

Extracellular Vesicles ◽

Pancreatic Beta Cells ◽

Neutralizing Antibodies ◽

Pancreatic Beta Cell ◽

Virus Production ◽

Size Exclusion ◽

Infectious Dose ◽

Viral Spread

While human enteroviruses are generally regarded as a lytic virus, and persistent non-cytolytic enterovirus infection in pancreatic beta cells has been suspected of playing a role in type 1 diabetes pathogenesis. However, it is still unclear how enteroviruses could exit the pancreatic beta cell in a non-lytic manner. This study aimed to investigate the role of beta cell-derived extracellular vesicles (EVs) in the non-lytic enteroviral spread and infection. Size-exclusion chromatography and antibody-based immunoaffinity purification were used to isolate EVs from echovirus 16-infected human beta EndoC-βH1 cells. EVs were then characterized using transmission electron microscopy and Multiplex Bead-Based Flow Cytometry Assay. Virus production and release were quantified by 50% cell culture infectious dose (CCID50) assay and qRT-PCR. Our results showed that EVs from echovirus 16-infected EndoC-βH1 cells harbor infectious viruses and promote their spread during the pre-lytic phase of infection. Furthermore, the EVs-mediated infection was not inhibited by virus-specific neutralizing antibodies. In summary, this study demonstrated that enteroviruses could exit beta cells non-lytically within infectious EVs, thereby thwarting the access of neutralizing antibodies to viral particles. These data suggest that enterovirus transmission through EVs may contribute to viral dissemination and immune evasion in persistently infected beta cells.

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Extracellular Vesicles From Liver Progenitor Cells Downregulates Fibroblast Metabolic Activity and Increase the Expression of Immune-Response Related Molecules

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.613583 ◽

2021 ◽

Vol 8 ◽

Author(s):

Felix Royo ◽

Mikel Azkargorta ◽

Jose L. Lavin ◽

Marc Clos-Garcia ◽

Ana R. Cortazar ◽

...

Keyword(s):

Progenitor Cells ◽

Cell Fate ◽

Extracellular Vesicles ◽

Mouse Liver ◽

Ribosome Biogenesis ◽

Transcript Expression ◽

Interacting Protein ◽

Related Response ◽

Mediate Cell ◽

Cell Crosstalk

Extracellular vesicles (EVs) mediate cell-to-cell crosstalk whose content can induce changes in acceptor cells and their microenvironment. MLP29 cells are mouse liver progenitor cells that release EVs loaded with signaling cues that could affect cell fate. In the current work, we incubated 3T3-L1 mouse fibroblasts with MLP29-derived EVs, and then analyzed changes by proteomics and transcriptomics. Results showed a general downregulation of protein and transcript expression related to proliferative and metabolic routes dependent on TGF-beta. We also observed an increase in the ERBB2 interacting protein (ERBIN) and Cxcl2, together with an induction of ribosome biogenesis and interferon-related response molecules, suggesting the activation of immune system signaling.

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miR-212/132-Enriched Extracellular Vesicles Promote Differentiation of Induced Pluripotent Stem Cells Into Pancreatic Beta Cells

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.673231 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chunyu Bai ◽

Qiwei Ren ◽

Haifeng Liu ◽

Xiangchen Li ◽

Weijun Guan ◽

...

Keyword(s):

Stem Cells ◽

Beta Cell ◽

Induced Pluripotent Stem Cells ◽

Beta Cells ◽

Extracellular Vesicles ◽

Pluripotent Stem Cells ◽

Pancreatic Beta Cells ◽

Pancreatic Beta Cell ◽

Induced Pluripotent

Pancreatic beta cell transplantation is the ideal method for treatment of type 1 diabetes mellitus (T1DM), and the generation of beta cells from induced pluripotent stem cells (iPSCs) of patients is a promising strategy. In this study, we improved a previous strategy to produce beta cells using extracellular vesicles (EVs) derived from mature beta cells and differentiated beta cells from iPSCs (i-Beta cells), which secreted insulin under glucose stimulation in vitro and ameliorated hyperglycemia in vivo. Mechanistic analyses revealed that EV-carried microRNA (miR)-212/132 (EV-miR-212/132) directly bound to the 3′ UTR of FBW7 to prevent its translation and FBW7 combined with NGN3 to accelerate its proteasomal degradation. EV-miR-212/132 stabilized NGN3 expression to promote differentiation of endocrine cells from induced iPSCs. Moreover, NGN3 bound to PDX1 to enhance transcription of endogenous miR-212/132 and formed a positive regulatory circuit that maintained the functions of mature pancreatic beta cells.ConclusionThis study describes a novel approach for beta cell production and supports the use of iPSCs for cell replacement therapy of T1DM.

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