Abstract:Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-der… Show more
“…However, in analogy with other aspects of EV bioprocessing, also the optimization of storage conditions and their impact on EV characteristics still require further research, which, in turn, demands larger amounts of available EVs …”
Potential applications of extracellular vesicles (EVs) are attracting increasing interest in the fields of medicine, cosmetics, and nutrition. However, the manufacturing of EVs is currently characterized by low yields. This limitation severely hampers progress in research at the laboratory and clinical scales, as well as the realization of successful and cost-effective EV-based products. Moreover, the high level of heterogeneity of EVs further complicates reproducible manufacturing on a large scale. In this review, possible directions toward the scalable production of EVs are discussed. In particular, two strategies are considered: i) the optimization of upstream unit operations and ii) the exploitation of well-established and mature technologies already in use in other industrial bioprocesses.
“…However, in analogy with other aspects of EV bioprocessing, also the optimization of storage conditions and their impact on EV characteristics still require further research, which, in turn, demands larger amounts of available EVs …”
Potential applications of extracellular vesicles (EVs) are attracting increasing interest in the fields of medicine, cosmetics, and nutrition. However, the manufacturing of EVs is currently characterized by low yields. This limitation severely hampers progress in research at the laboratory and clinical scales, as well as the realization of successful and cost-effective EV-based products. Moreover, the high level of heterogeneity of EVs further complicates reproducible manufacturing on a large scale. In this review, possible directions toward the scalable production of EVs are discussed. In particular, two strategies are considered: i) the optimization of upstream unit operations and ii) the exploitation of well-established and mature technologies already in use in other industrial bioprocesses.
“…Ultrafiltration utilises force to push the sample through the filter and is often used in combination with other techniques as it is more time efficient than centrifugation methods; however, there is the potential loss of EVs due to trapping in the pore membrane or non-specific binding of EVs to the membrane (Figure 2). While each isolation technique comes with its own limitations, there are ways to overcome those limitations and recommendations have been proposed previously [25,27–29]. 10.1080/20013078.2018.1522236-F0002Figure 2.Common methods in isolating the extracellular vesicles.…”
Through traditional medicine, there were diseases and disorders that previously remained untreated or were simply thought to be incurable. Since the discovery of mesenchymal stem cells (MSCs), there has been a flurry of research to develop MSC-based therapy for diseases and disorders. It is now well-known that MSCs do not typically engraft after transplantation and exhibit their therapeutic effect via a paracrine mechanism. In addition to secretory proteins, MSCs also produce extracellular vesicles (EVs), membrane-bound nanovesicles containing proteins, DNA and RNA. The secreted vesicles then interact with target cells and deliver their contents, imparting their ultimate therapeutic effect. Unlike the widely studied cancer cells, the yield of MSC-exosomes is a limiting factor for large-scale production for cell-free therapies. Here we summarise potential approaches to increase the yield of such vesicles while maintaining or enhancing their efficacy by engineering the extracellular environment and intracellular components of MSCs.
“…The complex function of LEVs revealed here in Giardia , suggests that their influence on phenotype could be even more diverse than those of SEVs (Tckach et al, 2018). No biomarkers were considered in the present study, since both EV populations are enriched mixtures of vesicles that fail to contain any unique marker (Kalra et al, 2013; Vader et al, 2016) and protozoa cells may have different sets of markers in their genome (Gonçalves et al, 2018; Ramirez et al, 2018).…”
Section: Discussionmentioning
confidence: 99%
“…Many reports have described the release of extracellular vesicles (EVs) from pathogens to be relevant to disease status (Cwiklinski et al, 2015; Coakley et al, 2017). EVs are found in most biological fluids and are 30-1000 nm lipid-bilayer vesicles, which are shed from cells and transport a range of biomolecules, participating in cell communication in physiological and pathophysiological processes (Coakley et al, 2015; Maas et al, 2017; van Niel et al, 2018; Ramirez et al, 2018; Ryu et al, 2018). Our group has previously described EV release of G. intestinalis and established that protozoa EVs are involved in pathogen interactions via immunomodulation and trophozoite persistence (Evans-Osses et al, 2017).…”
Giardia intestinalis is an anaerobic protozoan that is an important etiologic agent of inflammation-driven diarrhea worldwide. Although self-limiting, a deep understanding of the factors involved in the pathogenicity that produces the disruption of the intestinal barrier remains unknown. There is evidence that under diverse conditions, the parasite is capable of shedding extracellular vesicles (EVs) which could modulate the physiopathology of giardiasis. Here we describe new insights of G. intestinalis EV production, revealing its capacity to shed two different enriched EV populations (large and small extracellular vesicles) and identified a relevant adhesion function associated only with the larger population. Our work also aimed at assessing the influences of two recently identified inhibitors of EV release in mammalian cells, namely peptidylarginine deiminase (PAD) inhibitor and cannabidiol (CBD), on EV release from Giardia and their putative effects on host-pathogen interactions. PAD-inhibitor Cl-amidine and CBD were both able to effectively reduce EV shedding, the PAD-inhibitor specifically affecting the release of large extracellular vesicles and interfering with in vitro host-pathogen interactions. The strong efficacy of the PAD-inhibitor on Giardia EV release indicates a phylogenetically conserved pathway of PAD-mediated EV release, most likely affecting the Giardia arginine deiminase (GiADI) homolog of mammalian PADs. While there is still much to learn about G. intestinalis interaction with its host, our results suggest that large and small EVs may be differently involved in protozoa communication, and that EV-inhibitor treatment may be a novel strategy for recurrent giardiasis treatment.
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