Open AccessOverexpression of soluble RAGE in mesenchymal stem cells enhances their immunoregulatory potential for cellular therapy in autoimmune arthritis
Author(s) -
Min-Jung Park,
Jun Young Lee,
SuJin Moon,
Jung-Ah Lee,
Eunjung Lee,
Min Jung Kim,
JinSil Park,
Jennifer Lee,
JunKi Min,
Seok Jung Kim,
Sung-Hwan Park,
MiLa Cho
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep35933
Subject(s) - mesenchymal stem cell , rage (emotion) , proinflammatory cytokine , glycation , cancer research , arthritis , immunology , transplantation , cell therapy , rheumatoid arthritis , receptor , inflammation , chemistry , medicine , microbiology and biotechnology , stem cell , biology , neuroscience
Mesenchymal stem cells (MSCs) are attractive agents for cellular therapy in rheumatoid arthritis (RA). The receptor for advanced glycation end products (RAGE) serves as a pattern recognition receptor for endogenous inflammatory ligands. Soluble RAGE (sRAGE) is a truncated form of RAGE that functions as a decoy and acts as an anti-inflammatory molecule. The aim of this study was to determine whether sRAGE has therapeutic effects and the mechanisms active in sRAGE-overexpressing MSCs (sRAGE-MSCs) in an experimental model of RA. sRAGE-MSCs were generated by DNA transfection of human adipose tissue-derived MSCs (Ad-hMSCs). MSCs showed increased expression of VEGF , IL-1β , IL-6 , and HMGB-1 under inflammatory conditions. However, sRAGE-MSCs showed significantly lower production of these proinflammatory molecules. Expression of immunomodulatory molecules such as IL-10, TGF-β, and indoleamine 2, 3-dioxygenase was higher in sRAGE-MSCs than in mock-MSCs. sRAGE-MSCs showed enhanced migration potential. Transplantation of sRAGE-MSCs into arthritic IL-1Ra-knockout mice markedly suppressed inflammatory arthritis, decreased Th17 cells, and reciprocally increased regulatory T cells. The differentiation of IFN-γ + CD4 + and IL-17 + CD4 + cells was inhibited by incubation with sRAGE-MSCs compared with mock-MSCs. These findings suggest that sRAGE overexpression in Ad-hMSCs optimizes their immunoregulatory properties, which may be useful as a novel cellular therapy for RA.