Clinical application of tissue engineered human heart valves using autologous progenitor cells
Clinical application of tissue engineered human heart valves using autologous progenitor cells
复制标题
DOI：
10.1161/circulationaha.105.001065
复制
发表时间：
2006-07-04
期刊：
影响因子：
37.8
通讯作者：
Haverich, Axel
中科院分区：
文献类型：
--
作者：
Cebotari, Serghei;Lichtenberg, Artur;Haverich, Axel
背景-用自体细胞重新接种心脏瓣膜的组织工程（TE）已在体外成功进行。在这里，我们报告了我们首次临床植入用自体内皮祖细胞 (EPC) 改造的肺心瓣膜 (PV) 以及 3.5 年随访的结果。方法和结果 - 将人 PV 同种异体移植物脱细胞（胰蛋白酶/EDTA），并用从人血液中分离的外周单核细胞重新接种所得支架。在动态生物反应器系统的支架管腔表面上培养和分化长达 21 天的单层细胞中观察到冯维勒布兰德因子、CD31 和 Flk-1 的阳性染色，表明内皮性质。用自体细胞重新接种的 PV 被植入 2 名患有先天性 PV 衰竭的儿科患者（13 岁和 11 岁）体内。术后，两名儿童均出现轻度肺动脉瓣反流。根据定期超声心动图检查，血流动力学参数和心脏形态在 3.5 年内发生如下变化：PV 环直径增加（分别为 18 至 22.5 毫米和 22 至 26 毫米），瓣膜反流减少（分别为微不足道/轻度和微不足道），平均跨瓣压差减少（16 至 9 mm Hg）或增加（8 至 9.5 mm Hg），仍然为 26毫米或减小（32 至 28 毫米）右心室舒张末期直径。体表面积增加（分别为 1.07 至 1.42 m(2) 和 1.07 至 1.46 m(2)）。两名患者均未观察到瓣膜退变的迹象。结论-使用自体EPC进行人心脏瓣膜TE是一种可行且安全的肺动脉瓣置换方法。 TE 瓣膜有潜力根据儿童的体细胞生长进行重塑和生长。
Background-Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up.Methods and Results-Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m(2) and 1.07 to 1.46 m(2), respectively). No signs of valve degeneration were observed in both patients.Conclusions-TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.