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Endothelial Progenitor Cell (EPC) Recruitment in Rheumatoid Arthritis
Author(s) -
Silverman Matthew David,
Haas Christian S,
Rad Ali M,
Arbab Ali S,
Koch Alisa E
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a186
Subject(s) - medicine , homing (biology) , rheumatoid arthritis , neovascularization , chemokine , immunology , progenitor cell , arthritis , angiogenesis , cancer research , pathology , inflammation , stem cell , biology , microbiology and biotechnology , ecology
Marrow‐derived EPCs are important in the neovascularization occurring in diverse pathologies. In rheumatoid arthritis (RA), neovascularization of the joint's synovial lining propels disease by nourishing the inflamed and hyperproliferative synovial pannus, and begins even before clinical symptoms arise. We hypothesized that EPCs are selectively recruited to inflamed joints, and may perpetuate synovial neovascularization. In murine collagen‐induced arthritis (CIA) and anti‐collagen type II antibody‐induced arthritis models, we observed selective EPC recruitment to inflamed joints. In a chimeric severe compromised immunodeficient (SCID) mouse/human synovial tissue (ST) model, human EPCs homed selectively to subcutaneously engrafted human RAST vs normal ST. EPC adhesion to RA fibroblast (RAF) cultures and to RAST cryosections was dependent on the vascular cell adhesion molecule‐1 (VCAM‐1)/very late antigen‐4 (VLA‐4) adhesive system. RA synovial fluid, RA ST‐conditioned media, and the chemokines CXCL12 and CCL5 mediated EPC trafficking across RAF monolayers in vitro. These data demonstrate the selective recruitment of EPCs to inflamed joints and STs in diverse inflammatory arthritis models, and elucidate the adhesive and chemotactic mechanisms that govern EPC homing to RA tissues. These data support a likely role for EPCs in the synovial neovascularization that is critical to RA pathogenesis.