Siberian mouse like models3/6/2024 By applying these genetically modified immuno-susceptible murine systems, which are amenable to xenografting, we can directly implant human immune cells 12. In this context, humanized animal models using immunodeficient mice engrafted with cells or tissues from diseased patients are novel preclinical models for various pathologic conditions, including autoimmune diseases 11. However, most animal models have a limited ability to recapitulate the phenotypes and pathophysiologic mechanisms of SSc 10. The injection of type V collagen, a potential autoantigen in SSc, may induce SSc-like features 9. Rodents with mutations in genes related to signals causing fibrosis, such as friend leukemia integration 1 (Fli1)-deficient 5 or fos-related antigen 2 (Fra-2) transgenic (Tg) mice 6, 7, as well as naturally occurring tight skin 2 (Tsk2) mice 8, are used as animal models. Injecting exogenous bleomycin 3 or transplanting bone marrow into laboratory mice 4 induces skin fibrosis or graft-versus-host disease (GVHD) resembling SSc. Various animal models for SSc have been introduced. Because SSc is rare and its clinical manifestations are heterogeneous, an animal model recapitulating SSc features is needed to investigate the pathophysiologic mechanisms and evaluate the efficacy of potential therapeutics. There is no curative treatment for SSc 1, 2. Although skin involvement is one of the most prominent phenotypes, other organs, such as the heart, lungs, and kidneys, can also be affected, and their involvement is a prognostic factor for SSc 1, 2. 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. Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation, microangiopathy, and progressive fibrosis in the skin and internal organs.
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