Children's Hospital Boston and Harvard Medical School, Boston, Mass; Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
J Thorac Cardiovasc Surg. 2010 Mar;139(3):723-31. doi: 10.1016/j.jtcvs.2009.11.006.
Clinical translation of tissue-engineered heart valves requires valve competency and lack of stenosis in the short and long term. Early studies of engineered valves showed promise, although lacked complete definition of valve function. Building on prior experiments, we sought to define the in vivo changes in structure and function of autologous engineered pulmonary valved conduits.
Mesenchymal stem cells were isolated from neonatal sheep bone marrow and seeded onto a bioresorbable scaffold. After 4 weeks of culture, valved conduits were implanted. Valve function, cusp, and conduit dimensions were evaluated at implantation (echocardiography), at the experimental midpoint (magnetic resonance imaging), and at explant, at 1 day, and 1, 6, 12, or 20 weeks postoperatively (direct measurement, echocardiography). Histologic evaluation was performed.
Nineteen animals underwent autologous tissue-engineered valved conduit replacement. At implantation, valved conduit function was excellent; maximum transvalvular pressure gradient by Doppler echocardiography was 17 mm Hg; most valved conduits showed trivial pulmonary regurgitation. At 6 postoperative weeks, valve cusps appeared less mobile; pulmonary regurgitation was mild to moderate. At 12 weeks or more, valved conduit cusps were increasingly attenuated and regurgitant. Valved conduit diameter remained unchanged over 20 weeks. Dimensional measurements by magnetic resonance imaging correlated with direct measurement at explant.
We demonstrate autologous engineered tissue valved conduits that function well at implantation, with subsequent monitoring of dimensions and function in real time by magnetic resonance imaging. In vivo valves undergo structural and functional remodeling without stenosis, but with worsening pulmonary regurgitation after 6 weeks. Insights into mechanisms of in vivo remodeling are valuable for future iterations of engineered heart valves.
组织工程心脏瓣膜的临床转化需要在短期和长期内具有瓣膜功能和无狭窄。早期的工程瓣膜研究显示出了前景，尽管对瓣膜功能缺乏完整的定义。在前瞻性实验的基础上，我们试图确定自体工程肺动脉带瓣管道的结构和功能的体内变化。
从新生绵羊骨髓中分离间充质干细胞，并种植到生物可吸收支架上。培养 4 周后，植入带瓣管道。在植入时（超声心动图）、实验中点时（磁共振成像）以及在术后第 1 天、1 周、6 周、12 周和 20 周时（直接测量、超声心动图）评估瓣膜功能、瓣叶和管道尺寸。进行组织学评估。
19 只动物接受了自体组织工程带瓣管道置换。在植入时，带瓣管道功能良好；多普勒超声心动图测量的最大跨瓣压差为 17mmHg；大多数带瓣管道显示轻微的肺动脉瓣反流。术后 6 周时，瓣叶活动度降低；肺动脉瓣反流为轻度至中度。12 周或更久后，带瓣管道瓣叶逐渐变薄，反流加重。20 周内带瓣管道直径保持不变。磁共振成像的尺寸测量与离体的直接测量相关。
我们展示了自体工程组织瓣带瓣管道，在植入时功能良好，随后通过磁共振成像实时监测尺寸和功能。体内瓣膜经历结构和功能重塑而无狭窄，但在 6 周后出现肺动脉瓣反流加重。对体内重塑机制的深入了解对未来工程心脏瓣膜的迭代具有重要价值。
