Bioengineered self-seeding heart valves
Bioengineered self-seeding heart valves
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DOI：
10.1016/j.jtcvs.2011.10.005
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发表时间：
2012-01-01
影响因子：
6
通讯作者：
Yoo, James J.
中科院分区：
文献类型：
--
作者：
Jordan, James E.;Williams, J. Koudy;Yoo, James J.
目的：机械和生物假体用于替换受损的心脏瓣膜，但与显著的发病率相关。尽管人们对生物工程细胞种子心脏瓣膜支架越来越感兴趣，但这是一个耗时且技术困难的过程。这个项目的目标是设计自我播种的心脏瓣膜，在体内迅速成熟，准备时间更短。方法：用去垢法将猪肺动脉瓣去细胞化，然后(1)不处理（未偶联的，n = 6），(2)用自体内皮祖细胞衍生的内皮细胞重新播种（细胞播种的，n = 4），或(3)用CD133抗体偶联（偶联的，n = 8）。使用标准的外科技术将瓣膜结构移植到绵羊的肺位置。1或3个月后，取出植入物并评估细胞和基质含量以及生物力学性能。结果：在植入后1个月，表达血管性血血病因子的内皮细胞在共轭瓣膜的心室和动脉表面全部排列。随着金属蛋白酶-9的表达和新胶原的形成，1 ~ 3个月间瓣膜间质细胞和结构蛋白含量增加。相反，在任何时间点，几乎没有内皮细胞或间质细胞与未结合的或细胞种子瓣膜相关。任何瓣膜均未见钙化或血栓。杨氏模量和抗拉强度在共轭阀比非共轭或细胞种子阀更大。结论：结果表明，组织工程心脏瓣膜置换术可以快速完成，因此可能是需要及时进行心脏瓣膜手术的患者的临床相关选择。（中华胸心外科杂志；2012;43:201-8）
Objective: Mechanical and biological prostheses are used to replace damaged heart valves but are associated with significant morbidities. Although there is increased interest in bioengineering cell-seeded heart valve scaffolds, it is a time-consuming and technically difficult process. The goal of this project was to engineer self-seeding heart valves that mature quickly in vivo and have a shorter preparation time.Methods: Porcine pulmonary valves were decellularized using detergent methods and then either (1) left untreated (unconjugated, n = 6), (2) reseeded with autologous endothelial progenitor cell-derived endothelial cells (cell-seeded, n = 4), or (3) conjugated with CD133 antibodies (conjugated, n = 8). The valve constructs were transplanted into the pulmonary position of sheep using standard surgical techniques. After 1 or 3 months, the implants were removed and assessed for cell and matrix content as well as biomechanical properties.Results: Endothelial cells expressing von Willebrand factor lined the entire length of both ventricular and arterial surfaces of conjugated valves by 1 month after implantation. Interstitial cell and structural protein content of conjugated valves increased from 1 month to 3 months with interstitial expression of metalloproteinase-9 and new collagen formation. In contrast, there were few endothelial or interstitial cells associated with unconjugated, or cell-seeded valves at any time point. No calcification or thrombi were noted on any of the valves. Young's modulus and tensile strength was greater in the conjugated valves versus unconjugated or cell-seeded valves.Conclusions: Results indicate that tissue-engineered heart valve replacement constructs can be made quickly and therefore may be a clinically relevant option for patients needing heart valve surgery in a timely fashion. (J Thorac Cardiovasc Surg 2012;143:201-8)