Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation, microvasculopathy, and progressive fibrosis in multiple organs 1. Mice injected with patient-derived PBMCs show promise as an animal model of SSc. SSc hu-mice treated with rebamipide and other potential Th17-cell-modulating drugs presented significantly reduced tissue fibrosis. These cells showed increased expression of CXCR3 and phosphorylated STAT3. The proportions of circulating and tissue-infiltrating T helper 17 (Th17) cells were elevated in SSc hu-mice. Histological analysis of affected tissues from mice treated with SSc PBMCs (SSc hu-mice) demonstrated substantial inflammation, fibrosis and vasculopathy with human immune cell infiltration and increased expression of IL-17, TGF-β, CCL2, CC元, and CXCL9. Human PBMCs from SSc patients and healthy controls were engrafted into the blood, skin, and lung tissues of NSG mice. In addition, we investigated whether the humanized murine model could be used to assess the efficacy of potential therapeutics for SSc. Blood, skin, and lung tissues were acquired and analyzed after PBMC engraftment. Human PBMCs acquired from SSc patients and healthy controls were transferred into NOD.Cg- Prkdc scid Il2rg tm1Wjl (NSG) mice with concurrent bleomycin injection. Here, we introduce a novel animal model for SSc using immunodeficient mice injected with peripheral blood mononuclear cells (PBMCs) from SSc patients. To evaluate the pathophysiologic mechanisms and efficacies of potential therapeutics for SSc, a preclinical model recapitulating the disease phenotypes is needed. Boron neutron capture therapy (BNCT) is based on the ability of the boron-10 ( 10B) isotope to capture epithermal neutrons, as a result of which the isotope becomes unstable and decays into kinetically active elements that destroy cells where the nuclear reaction has occurred.Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation, microangiopathy, and progressive fibrosis in the skin and internal organs. The boron-carrying compounds-L-para-boronophenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH)-have low toxicity and, today, are the only representatives of such compounds approved for clinical trials. For the effectiveness and safety of BNCT, a low boron content in normal tissues and substantially higher content in tumor tissue are required. This study evaluated the boron concentration in intracranial grafts of human glioma U87MG cells and normal tissues of the brain and other organs of mice at 1, 2.5 and 5 h after administration of the boron-carrying compounds. A detailed statistical analysis of the boron biodistribution dynamics was performed to find a ‘window of opportunity’ for BNCT. The data demonstrate variations in boron accumulation in different tissues depending on the compound used, as well as significant inter-animal variation. The protocol of administration of BPA and BSH compounds used did not allow achieving the parameters necessary for the successful course of BNCT in a glioma orthotopic xenograft mouse model. Therapy for malignant tumors in the human brain is rather challenging. Despite considerable efforts to develop new drugs and treatments, patients’ mean overall survival has increased by only three months (from 12 to 15 months). Their invasive nature and location in vital regions of the human brain make these types of tumors difficult for surgery however, adjuvant therapy does not provide the desired results. Therefore, the elaboration of targeted radiotherapy methods is a promising approach for brain tumor therapy. One such treatment option may be boron neutron capture therapy (BNCT).īNCT exploits the ability of the isotope 10B to capture thermal neutrons and produce 478 keV γ rays, 4He particles and 7Li recoil ions, the latter two have high-linear energy transfer properties and a high biological effectiveness relative to photons. The range of these particles in tissue is restricted from 4 to 8 µm, thus limiting their effects to one cell diameter.
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