Leor J, Aboulafia-Etzion S, Dar A, Shapiro L, Barbash I M, Battler A, Granot Y, Cohen S
Cardiac Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Circulation. 2000 Nov 7;102(19 Suppl 3):III56-61. doi: 10.1161/01.cir.102.suppl_3.iii-56.
The myocardium is unable to regenerate because cardiomyocytes cannot replicate after injury. The heart is therefore an attractive target for tissue engineering to replace infarcted myocardium and enhance cardiac function. We tested the feasibility of bioengineering cardiac tissue within novel 3-dimensional (3D) scaffolds.
We isolated and grew fetal cardiac cells within 3D porous alginate scaffolds. The cell constructs were cultured for 4 days to evaluate viability and morphology before implantation. Light microscopy revealed that within 2 to 3 days in culture, the dissociated cardiac cells form distinctive, multicellular contracting aggregates within the scaffold pores. Seven days after myocardial infarction, rats were randomized to biograft implantation (n=6) or sham-operation (n=6) into the myocardial scar. Echocardiography study was performed before and 65+/-5 days after implantation to assess left ventricular (LV) remodeling and function. Hearts were harvested 9 weeks after implantation. Visual examination of the biograft revealed intensive neovascularization from the neighboring coronary network. Histological examination revealed the presence of myofibers embedded in collagen fibers and a large number of blood vessels. The specimens showed almost complete disappearance of the scaffold and good integration into the host. Although control animals developed significant LV dilatation accompanied by progressive deterioration in LV contractility, in the biograft-treated rats, attenuation of LV dilatation and no change in LV contractility were observed.
Alginate scaffolds provide a conducive environment to facilitate the 3D culturing of cardiac cells. After implantation into the infarcted myocardium, the biografts stimulated intense neovascularization and attenuated LV dilatation and failure in experimental rats compared with controls. This strategy can be used for regeneration and healing of the infarcted myocardium.
心肌无法再生，因为心肌细胞在损伤后不能复制。因此，心脏是组织工程的一个有吸引力的靶点，用于替代梗死心肌并增强心脏功能。我们测试了在新型三维（3D）支架内生物工程构建心脏组织的可行性。
我们在3D多孔藻酸盐支架内分离并培养胎儿心脏细胞。在植入前，将细胞构建体培养4天以评估活力和形态。光学显微镜显示，在培养2至3天内，解离的心脏细胞在支架孔隙内形成独特的多细胞收缩聚集体。心肌梗死后7天，将大鼠随机分为生物移植物植入组（n = 6）或假手术组（n = 6），植入心肌瘢痕内。在植入前和植入后65±5天进行超声心动图研究，以评估左心室（LV）重构和功能。植入9周后取出心脏。肉眼观察生物移植物显示，来自邻近冠状动脉网络的密集新生血管形成。组织学检查显示，肌纤维嵌入胶原纤维中，并有大量血管。标本显示支架几乎完全消失，并与宿主良好整合。尽管对照动物出现明显的左心室扩张，并伴有左心室收缩力逐渐恶化，但在生物移植物治疗的大鼠中，观察到左心室扩张减轻，左心室收缩力无变化。
藻酸盐支架提供了一个有利于心脏细胞三维培养的环境。与对照组相比，将生物移植物植入梗死心肌后，在实验大鼠中刺激了强烈的新生血管形成，并减轻了左心室扩张和衰竭。该策略可用于梗死心肌的再生和愈合。
