Published: Jan. 1, 2023

Oxygen (O2) concentration is important in both physiological and pathophysiological contexts. Modulating O2 vivo vitro challenging, yet has vast therapeutic potential necessary to accurately recapitulate environments, respectively. Herein, we developed O2-controlling strategies (i) boost vaccine immunogenicity, (ii) model tumor microenvironments vitro, (iii) understand cancer cell responses different low tensions. Using O2-generating cryogels (injectable, macroporous hydrogels), was used as an adjuvant immunogenicity protect against SARS-CoV-2. In mice, cryogel vaccines (O2-CryogelVAX) induced higher titers of neutralizing antibodies compared bolus (CryogelVAX), O2-CryogelVAX also increased B expansion draining lymph nodes (dLNs) IgG1 titer, suggesting that traveled the dLNs promoted germinal center formation. IgG sublcass cytokine characterization suggest generated a balanced Th1/Th2-mediated immune response without any signs allergic response. Our data represent promising platform increase context infectious disease.O2-controlled culture biological research method. One major use case study hypoxia, or O2. Widespread adoption this technique mitigated by cost, laboratory space requirements, technical challenges, rapid reoxygenation cultures. As alternative, hypothesized immobilizing glucose oxidase (GOX) catalase (CAT) matrices could simultaneously extracellular matrix (ECM) hypoxic environments vitro. After optimizing hypoxia-inducing (HIC) manufacturing process formulation, demonstrate HICs induce hypoxia (1% O2) for 11 days culture, with minimal hydrogen peroxide (H2O2) production consumption. future work, are utilized better dendritic polarization T interactions demonstrating their ability mimic microenvironment (TME). developing new method measure pericellular tension (i.e., cells experience) O2-controlled discovered physioxic (5% setpoints regularly anoxic (0% tensions adherent suspension Electron transport chain inhibition ablates effect, indicating cellular consumption driving factor. RNA-seq revealed primary human hepatocytes cultured physioxia experience ischemia-reperfusion injury due exposure followed reoxygenation. To relationship between incubator gas phase tensions, reaction-diffusion predicts priori. This effect greatest smaller volume vessels (e.g., 96-well plate). By controlling MCF7 have stronger glycolytic glutamine metabolism anoxia vs. hypoxia. expressed levels HIF2A, CD73, NDUFA4L2, etc. lower HIF1A, CA9, VEGFA, anoxia. Proteomics 4T1 had upregulated epithelial-to-mesenchymal transition (EMT) downregulated reactive oxygen species (ROS) management, glycolysis, fatty acid pathways Collectively, these results reveal breast respond non-monotonically O2, not suitable We atmospheric incubators insufficient control introduce concept culture. several modeling tissues physiologically, underpinning importance --Author's abstract

Language: Английский