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Nerviano, Italy

Carelli S.,University of Milan | Giallongo T.,University of Milan | Marfia G.,University of Milan | Merli D.,University of Milan | And 5 more authors.
Cell Transplantation

Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. Neural stem cells from the subventricular zone of the forebrain have been considered a potential tool for cell replacement therapies. We recently isolated a subclass of neural progenitors from the cadaver of mouse donors. These cells, named postmortem neural precursor cells (PM-NPCs), express both erythropoietin (EPO) and its receptor. Their EPO-dependent differentiation abilities produce a significantly higher percentage of neurons than regular NSCs. The cholinergic yield is also higher. The aim of the present study was to evaluate the potential repair properties of PM-NPCs in a mouse model of traumatic SCI. Labeled PM-NPCs were administered intravenously; then the functional recovery and the fate of transplanted cells were studied. Animals transplanted with PM-NPCs showed a remarkable improved recovery of hindlimb function that was evaluated up to 90 days after lesion. This was accompanied by reduced myelin loss, counteraction of the invasion of the lesion site by the inflammatory cells, and an attenuation of secondary degeneration. PM-NPCs migrate mostly at the injury site, where they survive at a significantly higher extent than classical NSCs. These cells accumulate at the edges of the lesion, where a reach neuropile is formed by MAP2- and b-tubulin III-positive transplanted cells that are also mostly labeled by anti-ChAT antibodies. © 2015 Cognizant Comm. Corp. Source

Russo M.,BU Oncology | Invernizzi A.,Istituto Zooprofilattico Sperimentale della Lombardia e dellEmila Romagna | Gobbi A.,Italian National Cancer Institute | Radaelli E.,University of Milan | Radaelli E.,Fondazione Filarete
Veterinary Pathology

This report describes the clinicopathological features of a case of diffuse scaling dermatitis that occurred in a 16-week-old female athymic nude (CrTac:NCr-Foxn1nu) mouse. Gross presentation was suggestive of Corynebacterium bovis infection (scaly skin disease). However, C. bovis was not isolated from the skin of the affected animal or from the skin of unaffected CrTac:NCr-Foxn1nu mice housed in the same cage or room. Staphylococcus xylosus was instead isolated in high numbers from the skin lesion, whereas only a few colonies were recovered from the skin of unaffected mice. Microscopically, the affected skin was characterized by chronic hyperplastic and hyperkeratotic dermatitis with focal ulcerations, extensive serocellular crusts, and intralesional clusters of Gram-positive coccoid bacteria. Although gross presentation of the reported case was suggestive of C. bovis infection, epidemiological, histopathological, and bacteriological findings definitively ruled out an outbreak of scaly skin disease. A diagnostic hypothesis of hyperplastic and hyperkeratotic dermatitis associated with opportunistic S. xylosus infection was formulated based on increased bacterial burden and presence of intralesional Gram-positive coccoid bacteria. © The Author(s) 2012. Source

Libani I.V.,University of Milan | Lucignani G.,University of Milan | Gianelli U.,University of Milan | Degrassi A.,BU Oncology | And 4 more authors.
Molecular Imaging and Biology

Purpose: We propose herein labeling protocols for multimodal in vivo visualization of human skeletal muscle cells (HSkMCs) by MRI and BLI to investigate the survival, localization, and proliferation/differentiation of these cells in cell-mediated therapy. Procedures: HSkMCs were labeled with different quantities of Endorem® and transfection agents or infected with lentiviral vector expressing the luciferase gene under the myogenin promoter. Cells were evaluated before and after intra-arterial injection in NUDE mice with N 2-induced muscle inflammation. Results: Neither iron labeling nor infection affected cell features; the number of iron-positive cells increased proportionally to the iron content in the medium and in the presence of transfection agents. Loaded cells were detected for up to 1 month by MRI and 2 months by BLI. Conclusions: These protocols could be used to visualize new stem cells, in vivo and over time, in preclinical studies of cell-based treatments for myopathies of different etiologies. © Academy of Molecular Imaging and Society for Molecular Imaging, 2011. Source

Martelli C.,University of Milan | Borelli M.,University of Milan | Ottobrini L.,University of Milan | Rainone V.,University of Milan | And 9 more authors.
Molecular Imaging and Biology

Purpose: The authors present a protocol for the in vivo evaluation, using different imaging techniques, of lymph node (LN) homing of tumor-specific dendritic cells (DCs) in a murine breast cancer model. Procedures: Bone marrow DCs were labeled with paramagnetic nanoparticles (MNPs) or 111In- oxine. Antigen loading was performed using tumor lysate. Mature DCs were injected into the footpads of transgenic tumor-bearing mice (MMTV-Ras) and DC migration was tracked by magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Ex vivo analyses were performed to validate the imaging data. Results: DC labeling, both with MNPs and with 111In-oxine, did not affect DC phenotype or functionality. MRI and SPECT allowed the detection of iron and 111In in both axillary and popliteal LNs. Immunohistochemistry and γ-counting revealed the presence of DCs in LNs. Conclusions: MRI and SPECT imaging, by allowing in vivo dynamic monitoring of DC migration, could further the development and optimization of efficient anti-cancer vaccines. © Academy of Molecular Imaging and Society for Molecular Imaging, 2011. Source

Albanese C.,BU Oncology | Alzani R.,BU Oncology | Amboldi N.,BU Oncology | Avanzi N.,BU Oncology | And 15 more authors.
Molecular Cancer Therapeutics

Altered expression and activity of cyclin-dependent kinase (CDK) and tropomyosin receptor kinase (TRK) families are observed in a wide variety of tumors. In those malignancies with aberrant CDK activation, the retinoblastoma protein (pRb) pathway is deregulated, leading to uncontrolled cell proliferation. Constitutive activation of TRKs is instead linked to cancer cell survival and dissemination. Here, we show that the novel small-molecule PHA-848125, a potent dual inhibitor of CDKs and TRKs, possesses significant antitumor activity. The compound inhibits cell proliferation of a wide panel of tumoral cell lines with submicromolar IC50. PHA-848125-treated cells show cell cycle arrest in G1 and reduced DNA synthesis, accompanied by inhibition of pRb phosphorylation and modulation of other CDK-dependent markers. The compound additionally inhibits phosphorylation of TRKA and its substrates in cells, which functionally express this receptor. Following oral administration, PHA-848125 has significant antitumor activity in various human xenografts and carcinogen-induced tumors as well as in disseminated primary leukemia models, with plasma concentrations in rodents in the same range as those found active in inhibiting cancer cell proliferation. Mechanism of action was also confirmed in vivo as assessed in tumor biopsies from treated mice. These results show that the dual CDK-TRK inhibitor PHA-848125 has the potential for being a novel and efficacious targeted drug for cancer treatment. ©2010 AACR. Source

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