Blood flow diverts extracellular vesicles from endothelial degradative compartments to promote angiogenesis
Benjamin Mary,
Nandini Asokan,
Katerina Jerabkova‐Roda
et al.
Abstract:Extracellular vesicles released by tumors (tEVs) disseminate via circulatory networks and promote microenvironmental changes in distant organs favoring metastatic seeding. Despite their abundance in the bloodstream, how hemodynamics affect the function of circulating tEVs remains unsolved. We demonstrated that efficient uptake of tEVs occurs in venous endothelial cells that are subjected to hemodynamics. Low flow regimes observed in veins partially reroute internalized tEVs toward non‐acidic and non‐degradativ… Show more
“…MemBright has been widely adopted by the extracellular vesicles community 51 to track extracellular vesicles both in vitro or in vivo in hippocampal 63 or cortical neurons, 79 zebrafish, 62,67,72 breast cancer cells or tumours, 66,71,80 myotubes, 82 and red blood cells. 74,76 Particle size distribution and zeta potential analysis of EVs derived from A375 cells using nanoparticle tracking analysis (NTA) showed that EVs labeled before and after labeling by MemBright have almost no change in size and only a slight shift of zeta potential.…”
Imaging neuronal architecture has been a recurrent challenge over the years, and the localization of synaptic proteins is a frequent challenge in neuroscience. To quantitatively detect and analyze the structure of synapses, we recently developed free SODA software to detect the association of pre and postsynaptic proteins. To fully take advantage of spatial distribution analysis in complex cells, such as neurons, we also selected some new dyes for plasma membrane labeling. Using Icy SODA plugin, we could detect and analyze synaptic association in both conventional and single molecule localization microscopy, giving access to a molecular map at the nanoscale level. To replace those molecular distributions within the neuronal three-dimensional (3D) shape, we used MemBright probes and 3D STORM analysis to decipher the entire 3D shape of various dendritic spine types at the singlemolecule resolution level. We report here the example of synaptic proteins within neuronal mask, but these tools have a broader spectrum of interest since they can be used whatever the proteins or the cellular type. Altogether with SODA plugin, MemBright probes thus provide the perfect toolkit to decipher a nanometric molecular map of proteins within a 3D cellular context.
“…MemBright has been widely adopted by the extracellular vesicles community 51 to track extracellular vesicles both in vitro or in vivo in hippocampal 63 or cortical neurons, 79 zebrafish, 62,67,72 breast cancer cells or tumours, 66,71,80 myotubes, 82 and red blood cells. 74,76 Particle size distribution and zeta potential analysis of EVs derived from A375 cells using nanoparticle tracking analysis (NTA) showed that EVs labeled before and after labeling by MemBright have almost no change in size and only a slight shift of zeta potential.…”
Imaging neuronal architecture has been a recurrent challenge over the years, and the localization of synaptic proteins is a frequent challenge in neuroscience. To quantitatively detect and analyze the structure of synapses, we recently developed free SODA software to detect the association of pre and postsynaptic proteins. To fully take advantage of spatial distribution analysis in complex cells, such as neurons, we also selected some new dyes for plasma membrane labeling. Using Icy SODA plugin, we could detect and analyze synaptic association in both conventional and single molecule localization microscopy, giving access to a molecular map at the nanoscale level. To replace those molecular distributions within the neuronal three-dimensional (3D) shape, we used MemBright probes and 3D STORM analysis to decipher the entire 3D shape of various dendritic spine types at the singlemolecule resolution level. We report here the example of synaptic proteins within neuronal mask, but these tools have a broader spectrum of interest since they can be used whatever the proteins or the cellular type. Altogether with SODA plugin, MemBright probes thus provide the perfect toolkit to decipher a nanometric molecular map of proteins within a 3D cellular context.
“…Third, EVs have a remarkable capacity to transverse biological barriers, such as bloodbrain barriers or endothelial barriers. [146][147][148] Although this feature holds significant therapeutic implications, how EVs accomplish this feat is still being elucidated, and whether this is true in higher primates is being debated and in humans, unknown. Proposed mechanisms include transcytosis (internalized by endothelial cells and subsequently released across the barrier) and EVmediated inflammation that disrupts tight junctions between endothelial cells and compromises barrier permeability.…”
From their humble discovery as cellular debris to cementing their natural capacity to transfer functional molecules between cells, the long-winded journey of extracellular vesicles (EVs) now stands at the precipice as a next-generation cell-free therapeutic tool to revolutionize modern-day medicine. This perspective provides a snapshot of the discovery of EVs to their emergence as a vibrant field of biology and the renaissance they usher in the field of biomedical sciences as therapeutic agents for cardiovascular pathologies. Rapid development of bioengineered EVs is providing innovative opportunities to overcome biological challenges of natural EVs such as potency, cargo loading and enhanced secretion, targeting and circulation half-life, localized and sustained delivery strategies, approaches to enhance systemic circulation, uptake and lysosomal escape, and logistical hurdles encompassing scalability, cost, and time. A multidisciplinary collaboration beyond the field of biology now extends to chemistry, physics, biomaterials, and nanotechnology, allowing rapid development of designer therapeutic EVs that are now entering late-stage human clinical trials.
The immune system is a highly complex and tightly regulated system that plays a crucial role in protecting the body against external threats, such as pathogens, and internal abnormalities, like cancer cells. It undergoes development during fetal stages and continuously learns from each encounter with pathogens, allowing it to develop immunological memory and provide a wide range of immune protection. Over time, after numerous encounters and years of functioning, the immune system can begin to show signs of erosion, which is commonly named immunosenescence. In this review, we aim to explore how the immune system responds to initial encounters with antigens and how it handles persistent stimulations throughout a person’s lifetime. Our understanding of the immune system has greatly benefited from advanced technologies like flow cytometry. In this context, we will discuss the valuable contribution of flow cytometry in enhancing our knowledge of the immune system behavior in aging, with a specific focus on T-cells. Moreover, we will expand our discussion to the flow cytometry-based assessment of extracellular vesicles, a recently discovered communication channel in biology, and their implications for immune system functioning.
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