IDEA #6O527J Amplified generation of exosomes by intercellular polymerization. 16A0031

Exosomes are nanoscale extracellular vesicles (30 – 100 nm), budding out from cells and carrying functional proteins RNAs/DNAs, actin fibers, and membranes. Recent studies revealed that exosome nanoparticles are actually specialized in long-distance intercellular communications between cell types, facilitating transfer of proteins, messenger RNAs (mRNAs), microRNAs, and DNAs from exosomes to recipient cells with high specificity, and transferring these genetic components to recipient cells. This genetic delivery between healthy cells could regulate cellular activities, however in some case it leads to the progression of nervous diseases, toxins, and cancers.1-3 For example, exosomes released from neuron facilitate diverse functions including removal of harmful stress proteins and amyloid fibril formation,4-6[85, 88, 89, 90] the therapeutic approaches have been proposed to control exosome generation for Parkinson’s disease and Alzheimer’s disease.7-9 For curdiovasucular activity, exosomes from cardiomyocytes (CMs) communicate with endotheilial cells (ECs) to generate neovasculature.10,11 The intercellular spreading of HIV and infectious prion were also found to be accelerated by exosomes.12-15 Recent reports shows that most types of cancer cells shed large numbers of exosomes that carry molecular information about the parent tumor,1 and cancer-derived exosomes could fuse with recipient cells thus influencing tumor progression.2,3 Some exosomes, for example derived from engineered immunotherapeutic cells (e.g., engineered T cells) and regenerative therapeutic cells (e.g., stem cells), are expected to be applied as “off-the-shelf” therapeutics because these exosomes that carry the same therapeutic proteins and genes from the parental cells are safer (i.e., exosomes are not viable) and incur less manufacturing and storage costs.16,17 Cancer cell-derived exosomes and microvesicles originated in the brain of glioma-bearing mice, and in patients with glioblastoma multiforme were detected in the blood circulation indicating their ability to cross the blood-brain barrier (BBB).18 Exosomes derived from bacterial pathogens have ben used for a long time for immunogenic vaccine against respective organisms even before the existence of exosomes is not clear.19 Therefore, the production of exosomes is important for practical medical applications of exosomes in broad medical areas, however the bottleneck of this approach is to mass-produce exosomes from parental cells.