Materials/Methods: Fluorescently labeled EV were isolated by the ultracentrifugation technique from conditioned medium collected from cultures of human stem cells (hESC or hNSC) or human neurons (GABAergic). Four-month-old athymic nude rats were divided into three groups: control (sham irradiation or surgery, n Z 8), irradiated undergoing sham surgery (10 Gy, n Z 8), and irradiated injected with EV (10 Gy, n Z 12). To test the translational application of this approach, EV were administered using intracranial (IC), retro-orbital vein (RO), or intranasal (IN) routes. Four to six week later potential therapeutic efficacy of EV in resolving radiation-induced cognitive deficits and electrophysiological properties of hippocampus was assessed. The brain tissues were fixed and sections imaged using confocal microscopy evaluating the hippocampus, prefrontal cortex, and subventricular zone. The yield fluorescent EV puncta was plotted as a function of administration route. For the lung fibrosis study, adult mice received whole thorax irradiation (14.4 Gy, n Z 18) and 24 h post-RT mice were divided in 2 groups 1) Control (n Z 7) and 2) treated group (n Z 11) with human embryonic stem cell (hESC)-derived EV injected via RO route. Results: Fluorescently-labeled EV were located and migrated through the CA1 stratum radium and granule cell molecular layers of the hippocampus, pre-limbic (PRL) and infra (IL) limbic structures of the PFC, and the SVZ. IC, RO and IN routes of administration were found to deliver qualitatively equivalent levels of EV to each subregion of the brain that were not found to be statistically different. Retro-orbital (RO) vein injection of GABAergic neuronal-derived EV was found to minimize radiation-induced reductions in hippocampal long-term potentiation (LTP). This data confirms our previous findings that stem cell-derived EV provided neurocognitive benefits in the irradiated brain. For the lung fibrosis study, EV-treated and irradiate animals were free of fibrosis, showed significant reductions in macrophage infiltration, inflammation and showed improved overall survival (91% versus 25%, p Z <0.0007). Conclusion: Findings demonstrate that targeted and systemic delivery of EV derived from various human cell sources can ameliorate normal tissue complications in the brain and lungs resulting from radiation exposures used to control malignant growth in the clinic. EV provide a potentially attractive therapeutic avenue for resolving normal tissue toxicities associated with radiotherapy.
AGAT, GAMT and CT1, three creatine synthesis and transport-related molecules, have been widely studied in mammals. To explore their homologous genes in adult zebrafish Danio rerio, the gene expression patterns of these three genes in D. rerio were investigated. The results reveal that AGAT, GAMT and CT1 are expressed widely in diverse tissues of D. rerio where the homologous genes in mammals are also expressed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.