Ramuscular transplantation of MSCs or exosomes in mdx mice Dopamine Receptor Antagonist supplier resulted in decreased creatine kinase level, decreased inflammatory cytokine expression and enhanced utrophin expression. Additionally, the PL-MSCs and PL-exosomes significantly decreased the level of fibrosis in the diaphragm and cardiac muscle tissues plus the expression of TGF-beta. Imaging analyses utilizing MSCs or exosomes labeled with fluorescent dyes demonstrated localization and engraftment of the cells and exosomes in the muscle tissues as much as four weeks post-treatment. Summary/Conclusion: These results demonstrate that PL-MSCs and their secreted exosomes have essential clinical applications in cell therapy of DMD partly by means of the delivery of exosomal miR-29 and targeting of multiples pathways including tissue fibrosis, inflammation and utrophin expression Funding: This function was funded by Israel Science Foundation, Adi, Science in Action and ExoSTem BiotecBackground: Extracellular vesicles (EVs) from stem cells (SCs) participate in tissue repair by transferring bioactive cargo. Even though, EVs from distinctive SCs were studied, the molecular profile and regenerative capacity of induced pluripotent SCs (iPS)- derived EVs (iPS-EVs) were not well investigated. The aim was to examine (1) phenotype and molecular content of iPSEVs, (two) their functional effect on mature target cells (cardiac and endothelial cells) in vitro, and (three) regenerative capacity in tissue injury models such as murine acute myocardial infarction (AMI) in vivo; and (four) biological properties of EVs kind iPS cells overexpressing procardioand proangiogenic miRNAs (miR-1, miR-199a and miR-126). Solutions: iPS cells were cultured in serum- and feeder-free conditions. miRNAs have been overexpressed by lentiviral transduction. iPS-EVs had been harvested from conditioned media by sequential centrifugation which includes ultracentrifugation (one hundred,000g). iPS-EV morphology and size were examined by AFM, NTA (Nanosight) and DLS (Izon), the antigen presence- by high-sensitivity FC (Apogee M-50) and WB, the mRNAs/miRNAs content- by real-time RT-PCR, the worldwide proteom -by mass spectrometry. Functional assays in target cells just after iPS-EV therapy in vitro involve: proliferation, migration, differentiation, metabolic activity and cell viability analyses. Regenerative prospective of iPS-EVs was examined in murine AMI model in vivo. Outcomes: We confirmed that iPS-EVs (1) contain iPS and exosomal markers; (two) are enriched in mRNAs, miRNAs and proteins from iPS cells regulating e.g. cell proliferation and differentiation; (3) transfer the cargo to target cells impacting on their functions in vitro; (four) exhibit regenerative possible by improving heart function following iPS-EV injection (at 35d). Importantly, no teratoma formation was identified in iPS-EVtreated animals. Summary/Conclusion: We showed that iPS-EVs: (1) carry and transfer bioactive content of iPS cells to heart cells improving their functions in vitro; (2) may possibly be enriched by genetic modifications of parental iPS cells, which enforce their activity; (three) improve heart repair in vivo. We conclude that iPS-EVs may perhaps represent new safe therapeutic tool in tissue regepair, option to whole iPS cells. Funding: This study was supported by CBP/p300 Activator manufacturer TEAM-2012/9-6 (FNP) to EZS and UMO-2013/10/E/NZ3/00750 (NCN) grants to EZS.OF14.Opioid-mediated extracellular vesicle production and NLRP3 inflammasome activation cause vascular damage Stephen R. Thom; Veena Bhopale; Kevin Yu; Ming Yang University of Maryland School of Medici.
