Reference and Translation Center for Cardiac Stem Cell Therapy, University of Rostock, Rostock, Germany.
Tissue Eng Part C Methods. 2011 Mar;17(3):299-309. doi: 10.1089/ten.TEC.2010.0051. Epub 2010 Nov 22.
The development of biological valve prostheses with lifetime native-like performance and optimal host engraftment is an ultimate goal of heart valve tissue engineering. We describe a new concept for autologous graft coating based on a CD133(+)-stem-cells-plus-fibrin (SC+F) complex processed from bone marrow and peripheral blood of a single patient.
CD133(+)-SC (1 × 10(6) cells/mL) from human bone marrow and autologous fibrin (20 mg/mL) were administered simultaneously via spray administration using the novel Vivostat Co-Delivery System. During static cultivation, SC+F performance was monitored for 20 days after delivery and compared with controls. For dynamic testing SC+F-composite was sprayed on a decellularized porcine pulmonary valve and transferred to a bioreactor under pulsatile flow conditions for 7 days.
Static cultivation of SC+F-composite induced significant improvements in stem cell proliferation as compared with controls. For dynamic testing, microscopic analyses on a smooth engineered heart valve surface detected homogenous distribution of stem cells. Ultrasonic analysis revealed native-like valve performance. Applied CD133(+) stem cells differentiated into endothelial-like cells positive for CD31 and vascular endothelial growth factor receptor 2 and engrafted the valve. However, occasional delamination was observed.
SC+F serves as an excellent autologous matrix for intraoperative tissue engineering of valve prostheses promising optimal in vivo integration. However, stability remains an issue.
开发具有终生原生性能和最佳宿主植入的生物瓣膜假体是心脏瓣膜组织工程的最终目标。我们描述了一种基于源自单个患者骨髓和外周血的 CD133(+)干细胞加纤维蛋白 (SC+F) 复合物的自体移植物涂层的新概念。
通过使用新型 Vivostat 共输送系统,同时以喷雾方式施用来自人骨髓的 CD133(+)SC(1×10(6)细胞/mL)和自体纤维蛋白(20mg/mL)。在输送后第 20 天,对 SC+F 的性能进行静态培养监测,并与对照进行比较。为了进行动态测试,将 SC+F 复合材料喷涂在脱细胞猪肺动脉瓣上,并在脉动流条件下转移到生物反应器中进行 7 天。
与对照组相比,SC+F 复合物的静态培养显著促进了干细胞的增殖。对于动态测试,在光滑的工程心脏瓣膜表面上进行的显微镜分析检测到干细胞的均匀分布。超声分析显示出类似于天然的瓣膜性能。应用的 CD133(+)干细胞分化为 CD31 和血管内皮生长因子受体 2 阳性的内皮样细胞,并植入瓣膜。然而,偶尔会观察到分层。
SC+F 是一种出色的自体基质,可用于术中瓣膜假体的组织工程,有望实现最佳的体内整合。然而,稳定性仍然是一个问题。