Inflammatory bowel disease (IBD) as a chronic recurrent disorder is characterized by mucosal immune response dysregulation, which is more prevalent in the youth. Adipose-derived mesenchymal stem cells (ADMSCs) are the multipotent cells that can be effective in immune response regulation via cell-cell interaction and their secretions. In this study, the effects of ADMSCs and mesenchymal stem cell-conditioned medium (MSC-CM) were evaluated on dextran sulfate sodium (DSS)-induced colitis in mice. Chronic colitis was induced in female C57BL/6 mice using 2% DSS in drinking water for three cycles; there were 4 days of DSS-water administration that was followed by 7 days of DSS-free water, in a cycle. ADMSCs, 10 cells per mouse, were injected intraperitoneally (IP), whereas the MSC-CM injection was also performed six times from the last day of DSS in Cycle 1. Clinical symptoms were recorded daily. The colon pathological changes, cytokine levels, and regulatory T (Treg) cell percentages were then analyzed. After receiving ADMSCs and MSC-CM in colitis mice, the clinical symptoms and disease activity index were improved and the survival rate was increased. The histopathological examination also showed tissue healing in comparison with the nontreated group. In addition, the increased level of transforming growth factor beta, increased percentage of Treg cells, increased level of interleukin (IL)-10, and decreased level of IL-17 were observed after the treatment. This study showed the regulatory effects of ADMSCs and MSC-CM on inflammatory responses. Therefore, the use of ADMSCs and MSC-CM can be introduced as a new and effective therapeutic approach for patients with colitis.
At the forefront of biopharmaceutical industry, the messenger RNA (mRNA) technology offers a flexible and scalable platform to address the urgent need for world-wide immunization in pandemic situations. This strategic powerful platform has recently been used to immunize millions of people proving both of safety and highest level of clinical efficacy against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we provide preclinical report of COReNAPCIN®; a vaccine candidate against SARS-CoV-2 infection. COReNAPCIN® is a nucleoside modified mRNA-based vaccine formulated in lipid nanoparticles (LNPs) for encoding the full-length prefusion stabilized SARS-CoV-2 spike glycoprotein on the cell surface. Vaccination of C57BL/6 and BALB/c mice and rhesus macaque with COReNAPCIN® induced strong humoral responses with high titers of virus-binding and neutralizing antibodies. Upon vaccination, a robust SARS-CoV-2 specific cellular immunity was also observed in both mice and non-human primate models. Additionally, vaccination protected rhesus macaques from symptomatic SARS-CoV-2 infection and pathological damage to the lung upon challenging the animals with high viral loads of up to 2 × 108 live viral particles. Overall, our data provide supporting evidence for COReNAPCIN® as a potent vaccine candidate against SARS-CoV-2 infection for clinical studies.
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