Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248

Abstract

CD248 (endosialin) belongs to a glycoprotein family that also includes thrombomodulin (CD141), CLEC14A, and CD93 (AA4) stem cell markers. We analyzed the regulated expression of CD248 in vitro using skin (HFFF) and synovial (FLS) mesenchymal stem cell lines, and in fluid and tissue samples of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells were incubated with either rhVEGF165, bFGF, TGF-β1, IL1-β, TNF-α, TGFβ1, IFN-γ, or PMA (Phorbol ester). There was no statistically significant change in membrane expression. A soluble (s) form of cleaved CD248 (sCD248) was detected after cell treatment with IL1-β and PMA. Matrix metalloprotease (MMP) MMP-1 and MMP-3 mRNAs were significantly up-regulated by IL1-β and PMA. A broad MMP inhibitor blocked the release of soluble CD248. In RA synovial tissue, we identified CD90+ perivascular MSCs double-stained for CD248 and VEGF. High sCD248 levels were detected in synovial fluid from RA. In culture, subpopulations of CD90+ CD14− RA MSCs were either identified as CD248+ or CD141+ cells but CD93−. CD248 is abundantly expressed by inflammatory MSCs and shed in an MMP-dependent manner in response to cytokines and pro-angiogenic growth factors. Both membrane-bound and soluble CD248 (acting as a decoy receptor) may contribute to RA pathogenesis.

On the origin and development of glioblastoma: multifaceted role of perivascular mesenchymal stromal cells

“…MSC express CD105 (Endoglin), CD73, and CD90 (Thy1) and lack the expression of CD45, CD34, CD14 or CD11b, CD79a or CD19, and HLA-DR [ 70 , 71 , 74 ]. Other markers, such as CD140b (PDGFRB), CD271 (Low-affinity NGF receptor), CD146 (Muc18), and CD248 have been suggested to identify MSC [ 75 – 78 ] but these markers are equally expressed by PC. As the concept of MSC was initially defined as a multipotent cell residing within the BM, it has evolved over the years to a wide concept that includes multipotent perivascular cells of any organ, including the CNS, as discussed below.…”