Rüger Beate, Giurea Alexander, Wanivenhaus Axel H, Zehetgruber Harald, Hollemann David, Yanagida Genya, Groger Marion, Petzelbauer Peter, Smolen Josef S, Hoecker Paul, Fischer Michael B
University of Vienna, Vienna, Austria.
Arthritis Rheum. 2004 Jul;50(7):2157-66. doi: 10.1002/art.20506.
To find evidence for the presence of endothelial precursor cells, which can induce new vessel formation, in the synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).
Precursor cells in the synovial tissue of 18 RA patients and 15 OA patients were identified by immunohistochemistry, morphometric analysis, and confocal laser scanning microscopy using the following phenotype markers: CD31, CD34, STRO-1, CD133, vascular endothelial growth factor receptor 2 (VEGFR-2), and CXCR4. The presence of CD31, CD34, CD133, VEGFR-2, and CXCR4 messenger RNA in the synovial tissue was determined by reverse transcriptase-polymerase chain reaction, and the message for CXCR4 was quantified by an RNase protection assay.
A population of cells that expressed CD34 on their surface but lacked the endothelial cell marker CD31 was found in the synovial tissue of RA and OA patients. CD34+,CD31- cells were detected in close proximity to STRO-1+ and CD133+ cells, forming cell clusters in the sublining area of the synovial membrane. Within these cell clusters, CD34+,CD31- precursor cells were located on the inside surrounded by STRO-1+ cells and with CD133+ cells on the outside. CD34+ precursor cells in the cell layer expressed high levels of the chemokine receptor CXCR4, while VEGFR-2 was expressed on CD34+ and CD133+ cells, and alpha-smooth muscle actin was expressed on STRO-1+ cells.
The presence of endothelial precursor cells in the synovial tissue of RA and OA patients provides evidence for vasculogenesis induced by precursor cells that arise in situ or from circulating progenitors.
探寻类风湿关节炎(RA)和骨关节炎(OA)患者滑膜组织中存在可诱导新血管形成的内皮祖细胞的证据。
采用免疫组织化学、形态计量分析和共聚焦激光扫描显微镜,利用以下表型标志物鉴定18例RA患者和15例OA患者滑膜组织中的祖细胞:CD31、CD34、STRO-1、CD133、血管内皮生长因子受体2(VEGFR-2)和CXCR4。通过逆转录聚合酶链反应测定滑膜组织中CD31、CD34、CD133、VEGFR-2和CXCR4信使核糖核酸的存在情况,并通过核糖核酸酶保护试验对CXCR4的信息进行定量分析。
在RA和OA患者的滑膜组织中发现一群表面表达CD34但缺乏内皮细胞标志物CD31的细胞。在紧邻STRO-1+和CD133+细胞处检测到CD34+、CD31-细胞,在滑膜衬里下层区域形成细胞簇。在这些细胞簇中,CD34+、CD31-祖细胞位于内部,被STRO-1+细胞包围,外部为CD133+细胞。细胞层中的CD34+祖细胞表达高水平的趋化因子受体CXCR4,而VEGFR-2在CD34+和CD133+细胞上表达,α-平滑肌肌动蛋白在STRO-1+细胞上表达。
RA和OA患者滑膜组织中存在内皮祖细胞,为原位产生或来自循环祖细胞的祖细胞诱导的血管生成提供了证据。