Bone marrow-derived mesenchymal stromal cells (MSCs) have attracted attention as potential platforms for the systemic delivery of therapeutic proteins in vivo following gene transfer using oncogenic retroviruses. However, the major limitations of this strategy include low levels of gene transfer and a general lack of long-term transgene expression. We have investigated the expression of several transgenes in MSCs following HIV-1 lentiviral vector-mediated gene transfer. Vectors containing a variety of strong promoters driving enhanced green fluorescence protein (EGFP) and coral (Discosoma sp.)-derived red fluorescent protein (DsRed) reporter genes pseudotyped with the vesicular stomatitis virus-G (VSV-G) glycoprotein were able to transduce cultured MSCs with high efficiency. Transduction efficiencies and transgene expression levels in MSCs were found to be higher with lentiviral vectors than with a vector based on the murine stem cell virus pseudotyped with VSV-G. Transgene expression was maintained in culture for at least 5 months. HIV-1-based lentiviral vectors were able to transduce clonogenic mesenchymal progenitor cells, which were capable of maintaining transgene expression by their MSC progeny, over several cell divisions and during differentiation into adipocytes, indicating that terminal adipocyte cell differentiation was unaffected by lentivirus-mediated reporter gene transfer. Collectively these results suggest that lentivirus-mediated gene transfer strategies provide an efficient tool for ex vivo modification of MSCs that does not interfere with differentiation.
Abstract. The photothermal ablation of solid tumors using exogenous, near-infrared ͑NIR͒-absorbing nanoparticles has been previously investigated using various preclinical models and is currently being evaluated in the clinic. Here, we evaluate the circulation kinetics, preliminary toxicity, and efficacy of photothermal ablation of solid tumors using gold nanorods systemically delivered and passively accumulated in a murine subcutaneous colon cancer model. Tumored animals were infused with nanorods followed by the percutaneous illumination of the tumor with an 808-nm laser. Control groups consisted of laser-only, nanorod-only, and untreated tumored animals. The survival of the treated and control groups were monitored for 60 days post-treatment. The survival of the photothermally treated group was statistically longer than the control groups, with approximately 44% tumor free through the evaluation period. Histopathology of the major organs of animals infused with nanorods did not indicate any significant toxicity at 60 days post-treatment. Particle biodistribution was evaluated by elemental analysis of the major organs of untumored mice at 1, 7, and 30 days after infusion with nanorods. Elemental analysis indicates nanorod clearance from the blood and retention by the reticuloendothelial system. This study indicates that gold nanorods are promising agents for photothermal ablation of solid tumors.
Inducible lentivirus vectors bearing insulators or second-generation TREs will likely prove useful for applications demanding the lowest levels of background expression.
With strong spin−orbit coupling (SOC), ultrathin two-dimensional (2D) transitional metal chalcogenides (TMDs) are predicted to exhibit weak antilocalization (WAL) effect at low temperatures. The observation of WAL effect in VSe 2 is challenging due to the relative weak SOC and three-dimensional (3D) transport nature in thick VSe 2 . Here, we report on the observation of quasi-2D transport and WAL effect in sublimed-salt-assisted low-temperature chemical vapor deposition (CVD) grown few-layered high-quality VSe 2 nanosheets. The WAL magnitudes in magnetoconductance can be perfectly fitted by the 2D Hikami−Larkin−Nagaoka (HLN) equation in the presence of strong SOC, by which the spin−orbit scattering length l SO and phase coherence length l ϕ have been extracted. The phase coherence length l ϕ shows a power law dependence with temperature, l ϕ ∼ T −1/2 , revealing an electron−electron interaction-dominated dephasing mechanism. Such sublimed-salt-assisted growth of high-quality few-layered VSe 2 and the observation of WAL pave the way for future spintronic and valleytronic applications.
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