A Perspective on the Characterization of Early Neural Progenitor Cell-Derived Extracellular Vesicles for Targeted Delivery to Neuroblastoma Cells.

As an element of the cellular signaling systems, extracellular vesicles (EVs) exhibit many desirable traits for usage as targeted delivery vehicles. When administered, EVs cause little to no toxic or immune response, stay in circulation for longer periods compared to synthetic carriers, preferentially accumulate in tissues that are the same or similar to their cell-of-origin and can pass through the blood-brain barrier. Combined, these traits make neural EVs a particularly promising tool for delivering drugs to the brain. This study aims to combine tissue and EVs engineering to prepare neural differentiated cells derived EVs that exhibit neural properties, to develop an effective, tissue-homing drug and gene delivery platform for the brain. Early neural differentiated cell-derived EVs were produced with neural characteristics from neural differentiated human neonatal dermal fibroblasts. The EVs carried key neural proteins such as Nestin, Sox2 and Doublecortin. The cellular uptake of early neural differentiated cell-derived EVs was higher compared to non-neural EVs during in vitro uptake assays on neuroblastoma cells. Moreover, eND-EVs were significantly decreased the viability of neuroblastoma cells. In conclusion, this study revealed that early neural differentiated cell-derived EVs have potential as a promising drug carrier for the treatment of various neural disorders.

Extracellular vesicles derived from human foreskin cells (hFS-Exo) accelerate cell migration and angiogenesis through MAPK pathway: an in vitro study.

BACKGROUND: Wound healing is one of the important processes in the body. Attempts to create new drugs are of interest due to the side effects of natural and chemical wound healing compounds. To overcome this obstacle, stem cells have been used as healing agents. However, both difficulties in collection and risks such as rejection and teratoma in the recipient body have limited the use of stem cells, directly. Since the potential content of the stem cells can be transferred to the recipient cells by vesicles, small extracellular vesicles have recently become prominent agents. METHODS AND RESULTS: The wound-healing effect of extracellular vesicles derived from foreskin cells was investigated in both keratinocyte and endothelial cells. Migration assay, RT-PCR, Col1a1 ELISA and Western Blot experiments were utilized to reveal healing effect of EVs and its possible molecular pathways. EV-treated groups exhibited more proliferative, invasive, and migrative characteristics. When comparing to the control group, new vessel formation was induced in EV groups. An increase in gene levels of growth factors related to wound healing and change in the mitogen-activated protein kinase (MAPK) signaling pathway proteins in EV-treated groups were determined. Possible molecular mechanisms underlying cell movements were associated with the MAPK pathway. It was found that human foreskin cell EVs (hFS-Exo) may have a potential to heal wounds in a short period of time by triggering the MAPK pathway. CONCLUSIONS: hFS-Exo could be a new promising wound healing agent in the future.

Unveiling the potential: Extracellular vesicles from plant cell suspension cultures as a promising source.

Extracellular vesicles are secreted by all eukaryotic cells and they have an important role in intercellular signaling. Plant extracellular vesicles (PEVs) are a novel area of research that has gained attention due to their potential implications in biomolecule transport and therapeutic applications. PEVs are lipid bilayer-enclosed structures that contain a diverse cargo of biomolecules such as proteins and lipids. Moreover, it is known that PEVs have a noticeable therapeutic potential for various conditions such as inflammation and oxidative stress. However, there are critical problems such as removing the endosomes and plant-derived biomolecules that decrease the standardization and therapeutic efficacy of PEVs. In our study, the aim was to characterize plant cell suspension-derived extracellular vesicles (PCSEVs) obtained from two different plant cell suspension cultures: Stevia rebaudiana and Vaccaria hispanica. These vesicles were isolated using ultrafiltration and characterized with nanoparticle tracking analysis (NTA) and atomic force microscopy (AFM). The molecular composition of PCSEVs was profiled and the cellular uptake assay was performed. Our results demonstrated that PCSEVs have a spherical shape, less than 200 nm. In the fatty acid analysis, the primary components in PCSEVs were palmitic acid, linoleic acid, and cis-vaccenic acid. The protein content of Stevia rebaudiana-derived EVs (SDEVs) was largely associated with proteins involved in extracellular structures and functions. Conversely, Vaccaria hispanica-derived EVs (HDEVs) displayed a higher presence of cytosolic proteins. These findings contribute to the understanding of PCSEVs and open up potential avenues in extracellular vesicle research, pointing to promising prospects for future innovations in various fields.

The emerging role of breast cancer derived extracellular vesicles-mediated intercellular communication in ovarian cancer progression and metastasis.

Breast cancer is one of the most occurring cancer types in women worldwide and metastasizes to several organs such as bone, lungs, liver, brain, and ovaries. Extracellular vesicles (EVs) mediate intercellular signaling which has a profound effect on tumor development and metastasis. Recent developments in the field of EVs provide an opportunity to investigate the roles of EVs released from tumor cells in metastasis. In this study, we compared the effects of metastatic breast cancer-derived EVs on both nonluteinized granulosa HGrC1 and ovarian cancer OVCAR-3 cells in terms of proliferation, invasion, apoptosis, and gene expression levels. EVs were isolated from the culture medium of metastatic breast cancer cell line MDA-MB-231 by ultracentrifugation. Cell proliferation, apoptosis, cell cycle, invasion, and cellular uptake analysis were performed to clarify the roles of tumor-derived EVs in both cells. 6.85 × 108 nanoparticles of BCD-EVs were markedly increased cell proliferation as well as invasion capacity. Exposing the cells with BCD-EVs for 24 h, resulted in an accumulation of both cells in G2/M phase as determined by flow cytometry. The apoptosis assay results were consistent with cell proliferation and cell cycle results. The uptake of the BCD-EVs was efficiently internalized by both cells. In addition, marked variations in fatty acid composition between cells were observed. BCD-EVs appeared new fatty acids in HGrC1. Besides, BCD-EVs upregulated epithelial-mesenchymal transition (EMT) and proliferation-related genes. In conclusion, an environment of tumor-derived EVs changes the cellular phenotype of cancer and noncancerous cells and may lead to tumor progression and metastasis.