We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Diabetes is accompanied by secretion of pro-atherosclerotic exosomes from vascular smooth muscle cells
Background
Atherosclerosis is a common co-morbidity of type 2 diabetes mellitus. Monocyte recruitment by an activated endothelium and the pro-inflammatory activity of the resulting macrophages are critical components of atherosclerosis. Exosomal transfer of microRNAs has emerged as a paracrine signaling mechanism regulating atherosclerotic plaque development. MicroRNAs-221 and -222 (miR-221/222) are elevated in vascular smooth muscle cells (VSMCs) of diabetic patients. We hypothesized that the transfer of miR-221/222 via VSMC-derived exosomes from diabetic sources (DVEs) promotes increased vascular inflammation and atherosclerotic plaque development.
Methods
Exosomes were obtained from VSMCs, following exposure to non-targeting or miR-221/-222 siRNA (-KD), isolated from diabetic (DVEs) and non-diabetic (NVEs) sources and their miR-221/-222 content was measured using droplet digital PCR (ddPCR). Expression of adhesion molecules and the adhesion of monocytes was measured following exposure to DVEs and NVEs. Macrophage phenotype following exposure to DVEs was determined by measuring mRNA markers and secreted cytokines. Age-matched apolipoprotein-E-deficient mice null (ApoE−/−) mice were maintained on Western diet for 6 weeks and received injections of saline, NVEs, NVE-KDs, DVEs or DVE-KDs every other day. Atherosclerotic plaque formation was measured using Oil Red Oil staining.
Results
Exposure of human umbilical vein and coronary artery endothelial cells to DVEs, but not NVEs, NVE-KDs, or DVE-KDs promoted increased intercellular adhesion molecule-1 expression and monocyte adhesion. DVEs but not NVEs, NVE-KDs, or DVE-KDs also promoted pro-inflammatory polarization of human monocytes in a miR-221/222 dependent manner. Finally, intravenous administration of DVEs, but not NVEs, resulted in a significant increase in atherosclerotic plaque development.
Conclusion
These data identify a novel paracrine signaling pathway that promotes the cardiovascular complications of diabetes mellitus.
Do different exosome biogenesis pathways and selective cargo enrichment contribute to exosomal heterogeneity?
Exosomes are emerging intercellular communicators essential for cellular homeostasis during development and differentiation. The dysregulation in exosome-mediated communication alters cellular networking leads to developmental defects and chronic diseases. Exosomes are heterogeneous in nature depending on differences in size, membrane protein abundance, and differential cargo load. In this review, we have highlighted the latest developments in exosome biogenesis pathways, heterogeneity, and selective enrichment of various exosomal cargoes including proteins, nucleic acids, and mitochondrial DNA. Furthermore, the recent developments in the isolation techniques of exosome subpopulations have also been discussed. The comprehensive knowledge of extracellular vesicle heterogeneity and selective cargo enrichment during specific pathology may provide a clue for disease severity and early prognosis possibilities. The release of specific exosome subtypes is associated with the progression of specific disease type and hence a probable tool for therapeutics and biomarker development. This article is protected by copyright. All rights reserved.
Isolation of bovine milk exosome using electrophoretic oscillation assisted tangential flow filtration
Tangent flow-driven ultrafiltration (TF-UF) is an efficient isolation process of milk exosomes without morphological deformation. However, the TF-UF approach with micro-ultrafiltration SiNx membrane filters suffers from the clogging and fouling of micro-ultrafiltration membrane filter pores with large bioparticles. Thus, it is limited in the long term, continuous isolation of large quantities of exosomes.
Exosomes: The Good, The Bad, and The Ugly
The last decade has seen an explosion of interest in regenerative medicine. From prolotherapy to platelet-rich plasma to stem cells, the quest to reverse disease has captured the attention of researchers worldwide. Interest in exosomes as an additional therapeutic option for osteoarthritis (OA) and neuropathy has also grown tremendously. Although originally thought to function as a cellular housekeeping tool, removing unwanted cellular waste,1 exosomes are now known to be involved in numerous biological processes and cell functions. These small vesicles have a long circulating half-life, can easily penetrate cell membranes, cross the blood-brain barrier, are hypo-immunogenic, and carry various “cargos” to their target cell.1-6 These factors, among many, are the drivers of research to unlock the potential of exosomes.
EXOSOMM Develops Proprietary Immune Supportive Natural Exosomes From Upcycled Whey
BioFoodTech start-up EXOSOMM, Ltd., has explored the natural mechanisms inherent in human breastmilk to create a novel bioactive ingredient that can potentially support millions of adults with inflammatory disorders. Based on its scientific findings EXOSOMM developed an innovative technology that isolates exosomes—natural particles in maternal milk that play an important role in the healthy development of the immune system.