Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.
Adv Drug Deliv Rev. 2016 Jan 15;96:103-9. doi: 10.1016/j.addr.2015.05.002. Epub 2015 May 14.
Cardiac tissue engineering is a promising therapeutic strategy for severe heart failure. However, conventional tissue engineering methods by seeding cells into biodegradable scaffolds have intrinsic limitations such as inflammatory responses and fibrosis arising from the degradation of scaffolds. On the other hand, we have developed cell sheet engineering as a scaffold-free approach for cardiac tissue engineering. Confluent cultured cells are harvested as an intact cell sheet using a temperature-responsive culture surface. By layering cardiac cell sheets, it is possible to form electrically communicative three-dimensional cardiac constructs. Cell sheet transplantation onto damaged hearts in several animal models has revealed improvements in heart functions. Because of the lack of vasculature, the thickness of viable cardiac cell sheet-layered tissues is limited to three layers. Pre-vascularized structure formation within cardiac tissue and multi-step transplantation methods has enabled the formation of thick vascularized tissues in vivo. Furthermore, development of original bioreactor systems with vascular beds has allowed reconstruction of three-dimensional cardiac tissues with a functional vascular structure in vitro. Large-scale culture systems to generate pluripotent stem cell-derived cardiac cells can create large numbers of cardiac cell sheets. Three-dimensional cardiac tissues fabricated by cell sheet engineering may be applied to treat heart disease and tissue model construction.
心脏组织工程是治疗严重心力衰竭的一种很有前途的治疗策略。然而，将细胞种植到可生物降解支架中的传统组织工程方法存在内在的局限性，例如支架降解引起的炎症反应和纤维化。另一方面，我们已经开发了无支架的细胞片层工程方法用于心脏组织工程。使用温度响应培养表面可以将培养的细胞片层作为一个完整的细胞片层收获。通过分层心脏细胞片，可以形成具有电连通性的三维心脏构建体。在几种动物模型中，将细胞片层移植到受损心脏上，显示出心脏功能的改善。由于缺乏脉管系统，有活力的心脏细胞片层组织的厚度限制在三层以内。在心脏组织内形成预血管化结构和多步移植方法，使得能够在体内形成厚的血管化组织。此外，具有血管床的原创生物反应器系统的开发允许在体外重建具有功能性血管结构的三维心脏组织。大规模培养系统生成多能干细胞来源的心脏细胞，可以产生大量的心脏细胞片。通过细胞片层工程制备的三维心脏组织可用于治疗心脏病和组织模型构建。
