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San Raffaele Open Research Data Repository

IRCCS San Raffaele Scientific Institute Showcase

San Raffaele Open Research Data Repository (ORDR) is an institutional platform which allows to store preserve and share research data. ORDR is powered by the Digital Commons Data repository platform.

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1970
2024
1970 2024
102 results
  • IL-10-producing regulatory cells impact on Celiac Disease evolution
    In the manuscript "IL-10-producing regulatory cells impact on celiac disease evolution" (doi: 10.1016/j.clim.2024.109923), we showed that IL-10-producing cells are fundamental in controlling pathological T-cell responses to gluten. In brief, our major findings are: 1) Gluten ingestion induces systemic inflammation in CD patients; 2) Gliadin-specific IFN-g+ T cells are present in patients regardless of tissue damage; 3) The presence of DC-10 in mucosal infiltrates is a hallmark of potential CD patients; 4) In potential CD, DC-10 maintain mucosal homeostasis and protect the gut from damage. The datasets here loaded contain all the clinical and immunological data, supporting our conclusions, that have been used to build the manuscript. An additional file (raw_data_description) contains the main guidelines to correctly associate the raw data with the corresponding figure/table in the manuscript.
    • Dataset
  • New orphan disease therapies from the proteome of industrial plasma processing waste- a treatment for aceruloplasminemia
    Raw data associated to the paper Zanardi, Nardini, et al. Communications Biology (see link). - Proteomics raw data for protein identification associated to Figure 1 of the manuscript are deposited in dedicated repository indicated in the paper (see "link") - Folder " 64CUkCP Biodistribution ": raw data associated to Fig 5 panel (a) and Supplementary Figure 8 describing labelled Cp biodistribution in the brain and blood of mice - Folder "Images choroid plexus": collection of the histochemistry images of choroid plexus stained for iron deposition used to generate data of figure 5 panels (g and h) - Folder "Images Purkinje": collection of the histochemistry images of cerbellum used to count thenumber of Purkinje neurons reported on figure 5 panels (i and j) - Folder "Images liver": collection of the histochemistry images of liver stained with hematoxylin-eosin used to generate figure 7 panels (c and d) - Folder Immunohistochemistry images Cerebellum => Autofluor Purkinje Cells Density: images used to generate data in figure 5 panels (k and l) - Folder Immunohistochemistry images Cerebellum => Astrocyte Density in Arbor Vitae: images used to generate data in figure 6 panels (a and b) - Folder Immunohistochemistry images Cerebellum => GFAP expression in Arbor Vitae: images used to generate data in figure 6 panel (c) - Folder Immunohistochemistry images Cerebellum => Microglia Density in Arbor Vitae: images used to generate data in figure 6 panels (a and d) - Folder Immunohistochemistry images Cerebellum => IBA1 expression in Arbor Vitae: images used to generate data in figure 6 panel (e) - Folder Immunohistochemistry images Hippocampus => Astrocyte Density in CA1 SR: images used to generate data in figure 6 panels (f and g) - Folder Immunohistochemistry images Hippocampus => GFAP expression in CA1 SR: images used to generate data in figure 6 panel (h) - Folder Immunohistochemistry images Hippocampus => Microglia Density in CA1 SR: images used to generate data in figure 6 panels (i and j) - Folder Immunohistochemistry images Hippocampus => IBA1 expression in CA1 SR: images used to generate data in figure 6 panel (k) - Folder Immunohistochemistry images Hippocampus => Neuron Density in CA1 SP: images used to generate data in figure 6 panels (l and m) - Folder Immunohistochemistry images Hippocampus => Thickness of CA1 SP: images used to generate data in figure 6 panel (n) - Folder Immunohistochemistry images Hippocampus => Autofluor Neurons Density in CA1 SP: images used to generate data in figure 6 panel (o) - Folder "WT+CP database ": raw data associated to Supplementary Figure 6 describing the evaluation of toxicity induction in wild-type (WT) mice treated for 4 months with purified ceruloplasmin
    • Dataset
  • Lipid dysmetabolism in ceruloplasmin-deficient mice revealed both in vivo and ex vivo by MRI, MRS and NMR analyses
    - Raw images of liver histological sections stained either with hematoxylin-eosin or with anti-F4/80 antigen antibody (counterstaining with hematoxylin) - Raw images of adipose tissue histological sections stained either with hematoxylin-eosin or with anti-F4/80 antigen antibody (counterstaining with hematoxylin) - Raw data from MRS and NMR spectra (files can be used with MestreNova software, Mestrelab Research, S.L. Santiago de Compostela, Spain)
    • Dataset
  • Partial correction of immunodeficiency by lentiviral vector gene therapy in mouse models carrying Rag1 hypomorphic mutations
    Recombination activating genes (RAG) 1 and 2 defects are the most frequent form of severe combined immunodeficiency (SCID). Patients with residual RAG activity have a spectrum of clinical manifestations ranging from Omenn syndrome to delayed-onset combined immunodeficiency, often associated with granulomas and/or autoimmunity (CID-G/AI). Lentiviral vector (LV) gene therapy (GT) has been proposed as an alternative treatment to the standard hematopoietic stem cell transplant and a clinical trial for RAG1 SCID patients recently started. However, GT in patients with hypomorphic RAG mutations poses additional risks, because of the residual endogenous RAG1 expression and the general state of immune dysregulation and associated inflammation. In this study, we assessed the efficacy of GT in 2 hypomorphic Rag1 murine models (Rag1F971L/F971L and Rag1R972Q/R972Q), exploiting the same LV used in the clinical trial encoding RAG1 under control of the MND promoter. Starting 6 weeks after transplant, GT-treated mice showed a decrease in proportion of myeloid cells and a concomitant increase of B, T and total white blood cells. However, counts remained lower than in mice transplanted with WT Lin- cells. At euthanasia, we observed a general redistribution of immune subsets in tissues, with the appearance of mature recirculating B cells in the bone marrow. In the thymus, we demonstrated correction of the block at double negative stage, with a modest improvement in the cortical/medullary ratio. Analysis of antigen-specific IgM and IgG serum levels after in vivo challenge showed an amelioration of antibody responses, suggesting that the partial immune correction could confer a clinical benefit. Notably, no overt signs of autoimmunity were detected, with B-cell activating factor decreasing to normal levels and autoantibodies remaining stable after GT. On the other hand, thymic enlargement was frequently observed, although not due to vector integration and insertional mutagenesis. In conclusion, our work shows that GT could partially alleviate the combined immunodeficiency of hypomorphic RAG1 patients and that extensive efficacy and safety studies with alternative models are required before commencing RAG gene therapy in these highly complex patients.
    • Dataset
  • Boosting Interleukin-12 Antitumor Activity and Synergism with Immunotherapy by Targeted Delivery with isoDGR-Tagged Nanogold
    Raw data and original images for the article entitled "Boosting Interleukin-12 Antitumor Activity and Synergism with Immunotherapy by Targeted Delivery with isoDGR-Tagged Nanogold" by Gasparri AM, Sacchi A, Basso V, Cortesi F, Freschi M, Rrapaj E, Bellone M, Casorati G, Dellabona P, Mondino A, Corti A, Curnis F. Small. 2019 Nov;15(45):e1903462. doi: 10.1002/smll.201903462.
    • Dataset
  • A fluorescent reporter model for the visualization and characterization of TDC
    TDC are hematopoietic cells that combine dendritic cell (DC) and conventional T cell markers and functional properties. They were identified in secondary lymphoid organs (SLOs) of naïve mice as cells expressing CD11c, major histocompatibility molecule (MHC)-II, and the T cell receptor (TCR)  chain. Despite thorough characterization as to their potential functional properties, a physiological role for TDC remains to be determined. Unfortunately, using CD11c as a marker for TDC has the caveat of its upregulation on different cells, including T cells, upon activation. Therefore, a more specific marker is needed to further investigate TDC functions in peripheral organs in different pathological settings. Here we took advantage of Zbtb46-GFP reporter mice to explore the frequency and localization of TDC in peripheral tissues at steady state and upon viral infection. RNA sequencing analysis confirmed that TDC identified with this reporter model have a gene signature that is distinct from conventional T cells and DC. In addition, frequency and total numbers of TDC in the SLOs recapitulated those found using CD11c as a marker. This reporter model allowed for identification of TDC in situ not only in SLOs but also in the liver and lung of naïve mice. Interestingly, we found that TDC numbers in the SLOs increased upon viral infection, suggesting that TDC might play a role during viral infections. In conclusion, we propose a visualization strategy that might shed light on the physiological role of TDC in several pathological contexts, including infection and cancer.
    • Dataset
  • NGR-TNF Engineering with an N‑Terminal Serine Reduces Degradation and Post-Translational Modifications and Improves Its Tumor-Targeting Activity
    Raw data and original images for the article entitled "NGR-TNF Engineering with an N-Terminal Serine Reduces Degradation and Post-Translational Modifications and Improves Its Tumor-Targeting Activity" by Angelo Corti, Anna Maria Gasparri, Angelina Sacchi, Barbara Colombo, Matteo Monieri, Eltjona Rrapaj, Andrés J. M. Ferreri, and Flavio Curnis Molecular Pharmaceutics 2020 17 (10), 3813-3824, DOI: 10.1021/acs.molpharmaceut.0c00579
    • Dataset
  • Genotoxic effects of base and prime editing in human hematopoietic stem cells
    Raw data associated to the manuscript by Fiumara et al. Base and prime editors (BEs and PEs) may provide more precise genetic engineering than nuclease-based approaches because they bypass the dependence on DNA double-strand breaks. However, little is known about their cellular responses and genotoxicity. Here, we compared state-of-the-art BEs and PEs and Cas9 in human hematopoietic stem and progenitor cells with respect to editing efficiency, cytotoxicity, transcriptomic changes and on-target and genome-wide genotoxicity. BEs and PEs induced detrimental transcriptional responses that reduced editing efficiency and hematopoietic repopulation in xenotransplants and also generated DNA double-strand breaks and genotoxic byproducts, including deletions and translocations, at a lower frequency than Cas9. These effects were strongest for cytidine BEs due to suboptimal inhibition of base excision repair and were mitigated by tailoring delivery timing and editor expression through optimized mRNA design. However, BEs altered the mutational landscape of hematopoietic stem and progenitor cells across the genome by increasing the load and relative proportions of nucleotide variants. These findings raise concerns about the genotoxicity of BEs and PEs and warrant further investigation in view of their clinical application.
    • Dataset
  • Hematopoietic reconstitution dynamics of mobilized- and bone marrow-derived human hematopoietic stem cells after gene therapy
    Mobilized peripheral blood is increasingly used instead of bone marrow as a source of autologous hematopoietic stem/progenitor cells for ex vivo gene therapy. Here, we present an unplanned exploratory analysis evaluating the hematopoietic reconstitution kinetics, engraftment and clonality in 13 pediatric Wiskott-Aldrich syndrome patients treated with autologous lentiviral-vector transduced hematopoietic stem/progenitor cells derived from mobilized peripheral blood (n=7), bone marrow (n=5) or the combination of the two sources (n=1). 8 out of 13 gene therapy patients were enrolled in an open-label, non-randomized, phase 1/2 clinical study(NCT01515462) and the remaining 5 patients were treated under expanded access programs. Although mobilized peripheral blood- and bone marrow- hematopoietic stem/progenitor cells display similar capability of being gene-corrected, maintaining the engineered grafts up to 3 years after gene therapy, mobilized peripheral blood-gene therapy group shows faster neutrophil and platelet recovery, higher number of engrafted clones and increased gene correction in the myeloid lineage which correlate with higher amount of primitive and myeloid progenitors contained in hematopoietic stem/progenitor cells derived from mobilized peripheral blood. In vitro differentiation and transplantation studies in mice confirm that primitive hematopoietic stem/progenitor cells from both sources have comparable engraftment and multilineage differentiation potential. Altogether, our analyses reveal that the differential behavior after gene therapy of hematopoietic stem/progenitor cells derived from either bone marrow or mobilized peripheral blood is mainly due to the distinct cell composition rather than functional differences of the infused cell products, providing new frames of references for clinical interpretation of hematopoietic stem/progenitor cell transplantation outcome. Data supporting the current study are part of a registered clinical trial (NCT01515462). These data are available under restricted access for the sensitive nature of the clinical data, access can be obtained by request to the corresponding author (Prof. Alessandro Aiuti, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, 20132 Italy.). We intend to reply to any requests within two weeks and we will share the deposited data only for research purposes. The non-clinical data generated in this study are also provided as the Source Data file associated to the published work.
    • Dataset
  • A comprehensive longitudinal study of magnetic resonance imaging identifies novel features of the Mecp2 deficient mouse brain
    Rett syndrome (RTT) is a X-linked neurodevelopmental disorder which represents the leading cause of severe incurable intellectual disability in females worldwide. The vast majority of RTT cases are caused by mutations in the X-linked MECP2 gene, and preclinical studies on RTT largely benefit from the use of mouse models of Mecp2, which present a broad spectrum of symptoms phenocopying those manifested by RTT patients. Neurons represent the core targets of the pathology; however, neuroanatomical abnormalities that regionally characterize the Mecp2 deficient mammalian brain remain ill-defined. Neuroimaging techniques, such as MRI and MRS, represent a key approach for assessing in vivo anatomic and metabolic changes in brain. Being non-invasive, these analyses also permit to investigate how the disease progresses over time through longitudinal studies. To foster the biological comprehension of RTT and identify useful biomarkers, we have performed a thorough in vivo longitudinal study of MRI and MRS in Mecp2 deficient mouse brains. Analyses were performed on both genders of two different mouse models of RTT, using an automatic atlas-based segmentation tool that permitted to obtain a detailed and unbiased description of the whole RTT mouse brain. We found that the most robust alteration of the RTT brain consists in an overall reduction of the brain volume. Accordingly, Mecp2 deficiency generally delays brain growth, eventually leading, in heterozygous older animals, to stagnation and/or contraction. Most but not all brain regions participate to the observed deficiency in brain size; similarly, the volumetric defect progresses diversely in different brain areas also depending on the specific Mecp2 genetic lesion and gender. Interestingly, in some regions volumetric defects anticipate overt symptoms, possibly revealing where the pathology originates and providing a useful biomarker for assessing drug efficacy in pre-clinical studies. DOI: 10.1016/j.nbd.2023.106083
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