Bensaïd W, Triffitt J T, Blanchat C, Oudina K, Sedel L, Petite H
Laboratoire de Recherches Orthopédiques, UMR-CNRS 7052, Faculté de Médecine Lariboisière Saint-Louis, Université D. Diderot, 10 avenue de Verdun, Paris 75010, France.
Biomaterials. 2003 Jun;24(14):2497-502. doi: 10.1016/s0142-9612(02)00618-x.
A potential therapy to enhance healing of bone tissue is to deliver isolated mesenchymal stem cells (MSCs) to the site of a lesion to promote bone formation. A key issue within this technology is the development of an injectable system for the delivery of MSCs. Fibrin gel exploits the final stage of the coagulation cascade in which fibrinogen molecules are cleaved by thrombin, convert into fibrin monomers and assembled into fibrils, eventually forming fibers in a three-dimensional network. This gel could have many advantages as a cell delivery vehicle in terms of biocompatibility, biodegradation and hemostasis. The objective of this study was to explore the possibility of using fibrin gel as a delivery system for human MSCs (HMSCs). To this end we have determined the optimal fibrinogen concentrations and thrombin activity for loading HMSCs in vitro into the resultant fibrin gels to obtain cell proliferation. We found that a concentration of 18 mg/ml of fibrinogen and a thrombin activity of 100 IU/ml was optimal for producing fibrin scaffolds that would allow good HMSCs spreading and proliferation. In these conditions, cells were able to proliferate and expressed alkaline phosphatase, a bone marker, in vitro. When implanted in vivo, HMSCs were able to migrate out of the fibrin gel and invade a calcium carbonate based ceramic scaffold suggesting that fibrin gel could serve as a delivery system for HMSCs.
一种促进骨组织愈合的潜在疗法是将分离的间充质干细胞（MSCs）输送到损伤部位以促进骨形成。该技术的一个关键问题是开发一种用于输送MSCs的可注射系统。纤维蛋白凝胶利用凝血级联反应的最后阶段，其中纤维蛋白原分子被凝血酶切割，转化为纤维蛋白单体并组装成纤维，最终在三维网络中形成纤维。这种凝胶作为细胞递送载体在生物相容性、生物降解性和止血方面可能具有许多优点。本研究的目的是探索使用纤维蛋白凝胶作为人MSCs（HMSCs）递送系统的可能性。为此，我们确定了将HMSCs体外加载到所得纤维蛋白凝胶中以实现细胞增殖的最佳纤维蛋白原浓度和凝血酶活性。我们发现，18mg/ml的纤维蛋白原浓度和100IU/ml的凝血酶活性最适合生产能够使HMSCs良好铺展和增殖的纤维蛋白支架。在这些条件下，细胞能够增殖并在体外表达碱性磷酸酶，一种骨标志物。当植入体内时，HMSCs能够从纤维蛋白凝胶中迁移出来并侵入基于碳酸钙的陶瓷支架，这表明纤维蛋白凝胶可以作为HMSCs的递送系统。
