Evaluation of a Peritoneal-Generated Cardiac Patch in a Rat Model of Heterotopic Heart Transplantation
Evaluation of a Peritoneal-Generated Cardiac Patch in a Rat Model of Heterotopic Heart Transplantation
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DOI：
10.3727/096368909788534898
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Leor, Jonathan
中科院分区：
文献类型：
--
作者：
Amir, Gabriel;Miller, Liron;Leor, Jonathan
组织工程学有望为心脏移植短缺和儿科心脏移植提供新的解决方案。这项研究的目的是评估在异位心脏移植模型中，腹膜生成的组织工程心脏补片替代受损心肌的能力。取同基因Lewis大鼠的胚胎心肌细胞(1×10(6)个/支架)种植于高孔度藻酸盐支架中。将构建的细胞体外培养4d后植入大鼠腹膜腔内1周。在此期间，植入腹膜的补片被血管化，并被肌成纤维细胞填充。在肾下异位腹部心脏移植模型(n=15)中检测它们的性能。供心移植后再灌流前，行左、右5 mm脑室切开6例或9例，将补片缝合于供心以修复缺损。移植后1-2周进行的超声心动图检查显示，在所研究的8个心脏中，有7个心脏左心功能正常。1个月后，移植补片的肉眼检查显示没有动脉瘤样扩张。显微镜检查显示，在大多数心脏补片中，支架完全消失，取而代之的是由嵌入胶原束的肌成纤维细胞组成的一致组织。心脏补片富含较多的浸润性血管。总之，在腹膜中产生的心脏补片被发展成具有封闭和纠正心肌缺陷的特性的一致的组织补片。我们的研究还为筛选和评估心脏重建和工程的新概念提供了一个可行的大鼠模型。
Tissue engineering holds the promise of providing new solutions for heart transplant shortages and pediatric heart transplantation. The aim of this study was to evaluate the ability of a peritoneal-generated, tissue-engineered cardiac patch to replace damaged myocardium in a heterotopic heart transplant model. Fetal cardiac cells (1 x 10(6)/scaffold) from syngeneic Lewis rats were seeded into highly porous alginate scaffolds. The cell constructs were cultured in vitro for 4 days and then they were implanted into the rat peritoneal cavity for 1 week. During this time the peritoneal-implanted patches were vascularized and populated with myofibroblasts. They were harvested and their performance in an infrarenal heterotopic abdominal heart transplantation model was examined (n = 15). After transplantation and before reperfusion of the donor heart, a 5-mm left (n = 6) or right (n = 9) ventriculotomy was performed and the patch was sutured onto the donor heart to repair the defect. Echocardiographical studies carried out 1-2 weeks after transplantation showed normal LV function in seven of the eight hearts studied. After I month, visual examination of the grafted patch revealed no aneurysmal dilatation. Microscopic examination revealed, in most of the cardiac patches, a complete disappearance of the scaffold and its replacement by a consistent tissue composed of myofibroblasts embedded in collagen bundles. The cardiac patch was enriched with a relatively large number of infiltrating blood vessels. In conclusion, cardiac patches generated in the peritoneum were developed into consistent tissue patches with properties to seal and correct myocardial defects. Our study also offers a viable rat model for screening and evaluating new concepts in cardiac reconstruction and engineering.