Verhagen H J, Heijnen-Snyder G J, Vink T, Pronk A, van Vroonhoven T J, Eikelboom B C, Sixma J J, de Groot P G
Department of Surgery, University Hospital Utrecht, The Netherlands.
Thromb Haemost. 1995 Oct;74(4):1096-102.
Lining the luminal surface of prosthetic small diameter bypasses with endothelial cells (EC) will lower its thrombogenicity. Unfortunately, human EC are only scarcely available. Mesothelial cells (MC) have antithrombotic properties in vivo and can be harvested in large numbers, from the omentum. Recent work demonstrated that the expression of tissue factor (TF) is induced in MC after isolation and culture. Different culture conditions were studied to suppress TF-expression. MC grown in pooled human serum (HS) are procoagulant (717 +/- 119 pM factor Xa/min.10(5) cells). Replacing HS for fetal calf serum, precoating the surface with extracellular matrix and the addition of the xanthine-oxidase inhibitor allopurinol, inhibited TF expression by 90% (p < 0.001). Allopurinol clearly reduced TF-mRNA levels. TF expression on cultured MC is an in-vitro effect due to culture conditions and the formation of oxygen free radicals. By reducing TF expression by 90%, we have established conditions in which MC are a good alternative for EC for seeding on synthetic grafts.
用人内皮细胞(EC)内衬人工小直径旁路的管腔表面可降低其血栓形成性。不幸的是,人内皮细胞很难获得。间皮细胞(MC)在体内具有抗血栓特性,并且可以从大网膜大量获取。最近的研究表明,间皮细胞在分离和培养后会诱导组织因子(TF)的表达。研究了不同的培养条件以抑制TF的表达。在混合人血清(HS)中生长的间皮细胞具有促凝血性(717±119 pM因子Xa/分钟·10⁵个细胞)。用胎牛血清替代人血清、用细胞外基质预包被表面以及添加黄嘌呤氧化酶抑制剂别嘌呤醇,可使TF表达抑制90%(p<0.001)。别嘌呤醇明显降低了TF-mRNA水平。培养的间皮细胞上TF的表达是由于培养条件和氧自由基形成导致的一种体外效应。通过将TF表达降低90%,我们建立了这样的条件,即间皮细胞是用于接种在合成移植物上的内皮细胞的良好替代物。