12 research outputs found

    Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma

    Get PDF
    Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced apoptosis in co-cultured human glioblastoma cells. Time-lapse imaging shows that iNSCs are tumouritropic, homing rapidly to co-cultured glioblastoma cells and migrating extensively to distant tumour foci in the murine brain. Multimodality imaging reveals that iNSC delivery of the anticancer molecule TRAIL decreases the growth of established solid and diffuse patient-derived orthotopic glioblastoma xenografts 230- and 20-fold, respectively, while significantly prolonging the median mouse survival. These findings establish a strategy for creating autologous cell-based therapies to treat patients with aggressive forms of brain cancer

    All-sky measurement of the anisotropy of cosmic rays at 10 TeV and mapping of the local interstellar magnetic field

    No full text
    We present the first full-sky analysis of the cosmic ray arrival direction distribution with data collected by the High-Altitude Water Cherenkov and IceCube observatories in the northern and southern hemispheres at the same median primary particle energy of 10 TeV. The combined sky map and angular power spectrum largely eliminate biases that result from partial sky coverage and present a key to probe into the propagation properties of TeV cosmic rays through our local interstellar medium and the interaction between the interstellar and heliospheric magnetic fields. From the map, we determine the horizontal dipole components of the anisotropy δ 0h = 9.16 × 10−4 and δ 6h = 7.25 × 10−4 (±0.04 × 10−4). In addition, we infer the direction (229fdg2 ± 3fdg5 R.A., 11fdg4 ± 3fdg0 decl.) of the interstellar magnetic field from the boundary between large-scale excess and deficit regions from which we estimate the missing corresponding vertical dipole component of the large-scale anisotropy to be δN3.972.0+1.0×104{\delta }_{N}\sim -{3.97}_{-2.0}^{+1.0}\times {10}^{-4}

    One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina

    No full text
    corecore