| Literature DB >> 24762627 |
Mehmet E Yalvac1, William David Arnold2, Syed-Rehan A Hussain3, Cilwyn Braganza3, Kimberly M Shontz3, Kelly Reed Clark1, Christopher M Walker4, Eroboghene E Ubogu5, Jerry R Mendell6, Zarife Sahenk7.
Abstract
The spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7-2 knockout nonobese diabetic mice mimics a progressive and unremitting course of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, bone marrow-derived dendritic cells (DCs) were transduced to express vasoactive intestinal polypeptide (VIP) using a lentiviral vector (LV-VIP). These transduced DCs (LV-VIP-DCs) were then injected intravenously (i.v.) into 16-week-old (before disease onset) and 21-week-old (after disease onset) SAPP mice in order to prevent or attenuate the disease. Outcome measures included behavioral tests, clinical and histological scoring, electrophysiology, real-time PCR, flow cytometry analyses, and enzyme-linked immunosorbent assay. LV-VIP-DCs were recruited to the inflamed sciatic nerve and reduced the expression of inflammatory cytokines. A single injection of LV-VIP-DC delayed the onset of disease, stabilized, and attenuated clinical signs correlating with ameliorated behavioral functions, reduced nerve demyelination, and improved nerve conduction. This proof-of-principle study is an important step potentially leading to a clinical translational study using DCs expressing VIP in cases of CIDP refractory to standard immunosuppressive therapy.Entities:
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Year: 2014 PMID： 24762627 PMCID： PMC4089012 DOI： 10.1038/mt.2014.77
Source DB: PubMed Journal: Mol Ther ISSN： 1525-0016 Impact factor: 11.454