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Cell Journal، جلد ۱۹، شماره ۳، صفحات ۳۶۱-۳۷۵
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عنوان انگلیسی Multiple Sclerosis Gene Therapy with Recombinant Viral Vectors: Overexpression of IL-4, Leukemia Inhibitory Factor, and IL-10 in Wharton’s Jelly Stem Cells Used in EAE Mice Model
چکیده انگلیسی مقاله Objective: Autoimmune disease (AD) caused by unbalanced expression of cytokines in patients lead to chronic inflammatory. Many ADs start with chronic inflammatory in human organs that lead to destroying crucial human cells and tissues. Wharton’s jelly stem cells (WJSCs) with pluripotent and immunomodulatory properties emerge as the novel source for cell therapy. Anti-inflammatory cytokines like interleukin 4 (IL-4), leukemia inhibitory factor (LIF) and interleukin 10 (IL-10) promised as a novel candidates for autoimmune gene therapy. Multiple sclerosis (MS) with current treatments is only manageable, neither preventable nor reversible. MS treatment needs an effective approach like stem cells and gene therapy. Materials and methods: DNA construction contained IL-4, IL-10 and LIF was assembled as a polycistronic vector (transfer vector). Transfer and control vector were co-transfect into HEK-293T cells with helper plasmids to producing recombinant lentiviral viruses (rLV). WJSCs were transducted with rLV to make recombinant WJSC (rWJSC). In-vitro protein and mRNA overexpression of IL-4, LIF, and IL-10 evaluated with qPCR, ELISA and WB. Experimental autoimmune encephalomyelitis (EAE) induced in mice with MOG-CFA and pertussis toxin. EAE mice were injected twice with 2*105 rWJSC cells. The in-vivo level of IL-4, LIF, and IL-10 cytokines and Il-17 were measured with ELISA. Brain tissues were analyzed histologically for evaluating of EAE lesion reduction. Results: Isolated WJSCs were confirmed by in-vitro differentiation and surface marker analyzed with flow cytometry. Cloning of single lentiviral vector with five genes was done successfully. Transfection of transfer and control vectors were processed with the CaPo4 method in high efficiency (above 90%). Recombinant viruses were produced and the result of titration showed 2-3*107 infection-unit/ml. WJSCs were transducted with recombinant viruses and IL-4, IL-10 and LIF overexpression were confirmed with ELISA, WB and qPCR. EAE mice model treatment with rWJSC showed the reduction of in-vivo Il-17, brain lesions and infiltrate cell foci. Weight and physical activity were improved in gene therapy treated group. Conclusion: These results showed that gene therapy with anti-inflammatory cytokines can be a promising approach for MS treatment. In addition, combination of immunomodulatory potential of WJSC with gene therapy improved efficiency of the treatment.
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نویسندگان مقاله | Ahmad Hosseini


| Hajar Estiri


| Haleh Akhavan Niaki


| Akram Alizadeh


| Baharak Abdolhossein zadeh


| Sayyed Mohammad Ghaderian


| Akbar Farjadfar


| Ali Fallah


نشانی اینترنتی http://celljournal.org/journal/article/abstract/4497
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