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Effect of extracellular vesicles on cancer cell lines in vitro and biodistribution in an ectopic osteosarcoma mouse modelJavier, Abello January 1900 (has links)
Doctor of Philosophy / Department of Food, Nutrition, Dietetics and Health / Tonatiuh Melgarejo / Mark Haub / Human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) have an enormous therapeutic potential because of their immunomodulatory and anti-inflammatory properties. However, there are limitations for their therapeutic use due to low cell survival after implantation, the risk of culture-borne pathogens, and the risk of embolism and thrombosis after intravenous infusion. Exosomes, on the other hand, constitute an important part of the MSCs secretome and may play a role in their therapeutic effects. Here, it was demonstrated that HUC-MSC-derived exosomes accumulate in human and mouse osteosarcoma cell lines in vitro and reduce their proliferation. The distribution of HUC-MSCs exosomes was shown in osteosarcoma tumor- bearing mice. Exosome distribution in vivo was observed using Magnetic Resonance Imaging (MRI) of gadolinium-labeled exosomes and by fluorescent imaging after infusion of near infrared dye-labeled exosomes. HUC-MSC exosomes accumulated in the tumor throughout the 48 hours ours post-injection period. In contrast, synthetic lipid nanoparticle accumulate in tumor only for the first 3ours post-injection. These results suggest that labeling with gadolinium or near-infrared dye may affect exosome accumulation within the spleen. In summary, this study showed that HUC-MSCs exosomes can accumulate to osteosarcoma cells in vitro and in vivo, and thus they may be useful for detecting cancer metastasis.
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