Amir Gabriel, Miller Liron, Shachar Michal, Feinberg Micha S, Holbova Radka, Cohen Smadar, Leor Jonathan
Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer, Israel.
Cell Transplant. 2009;18(3):275-82. doi: 10.3727/096368909788534898.
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 1 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.
组织工程有望为心脏移植短缺和小儿心脏移植提供新的解决方案。本研究的目的是评估一种腹膜生成的组织工程心脏补片在异位心脏移植模型中替代受损心肌的能力。将同基因Lewis大鼠的胎儿心脏细胞(1×10⁶/支架)接种到高度多孔的藻酸盐支架中。细胞构建体在体外培养4天,然后植入大鼠腹腔1周。在此期间,腹膜植入的补片血管化并充满肌成纤维细胞。将它们收获并在肾下异位腹部心脏移植模型中检测其性能(n = 15)。在供体心脏移植后再灌注前,进行5毫米的左心室(n = 6)或右心室(n = 9)切开术,并将补片缝合到供体心脏上以修复缺损。移植后1 - 2周进行的超声心动图研究显示,在所研究的8颗心脏中有7颗左心室功能正常。1个月后,对移植补片的肉眼检查未发现动脉瘤样扩张。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中的肌成纤维细胞组成的一致组织。心脏补片富含相对大量的浸润血管。总之,在腹膜中生成的心脏补片发展成为具有密封和纠正心肌缺损特性的一致组织补片。我们的研究还提供了一种可行的大鼠模型,用于筛选和评估心脏重建与工程中的新概念。