Shimizu Tatsuya
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University.
Circ J. 2014;78(11):2594-603. doi: 10.1253/circj.cj-14-0973. Epub 2014 Oct 16.
In addition to stem cell biology, tissue engineering is an essential research field for regenerative medicine. In contrast to cell injection, bioengineered tissue transplantation minimizes cell loss and has the potential to repair tissue defects. A popular approach is scaffold-based tissue engineering, which utilizes a biodegradable polymer scaffold for seeding cells; however, new techniques of cell sheet-based tissue engineering have been developed. Cell sheets are harvested from temperature-responsive culture dishes by simply lowering the temperature. Monolayer or stacked cell sheets are transplantable directly onto damaged tissues and cell sheet transplantation has already been clinically applied. Cardiac cell sheet stacking produces pulsatile heart tissue; however, lack of vasculature limits the viable tissue thickness to 3 layers. Multistep transplantation of triple-layer cardiac cell sheets cocultured with endothelial cells has been used to form thick vascularized cardiac tissue in vivo. Furthermore, in vitro functional blood vessel formation within 3-dimensional (3D) tissues has been realized by successfully imitating in vivo conditions. Triple-layer cardiac cell sheets containing endothelial cells were layered on vascular beds and the constructs were media-perfused using novel bioreactor systems. Interestingly, cocultured endothelial cells migrate into the vascular beds and form perfusable blood vessels. An in vitro multistep procedure has also enabled the fabrication of thick, vascularized heart tissues. Cell sheet-based tissue engineering has revealed great potential to fabricate 3D cardiac tissues and should contribute to future treatment of severe heart diseases and human tissue model production.
除了干细胞生物学外,组织工程学也是再生医学的一个重要研究领域。与细胞注射不同,生物工程组织移植可将细胞损失降至最低,并具有修复组织缺损的潜力。一种常用的方法是基于支架的组织工程,该方法利用可生物降解的聚合物支架来接种细胞;然而,基于细胞片的组织工程新技术已经得到发展。通过简单地降低温度,可从温度响应培养皿中收获细胞片。单层或堆叠的细胞片可直接移植到受损组织上,并且细胞片移植已经在临床上得到应用。心脏细胞片堆叠可产生搏动性心脏组织;然而,缺乏血管系统将存活组织的厚度限制在3层。与内皮细胞共培养的三层心脏细胞片的多步移植已被用于在体内形成厚的血管化心脏组织。此外,通过成功模拟体内条件,已在三维(3D)组织内实现了体外功能性血管形成。将含有内皮细胞的三层心脏细胞片铺在血管床上,并使用新型生物反应器系统对构建体进行介质灌注。有趣的是,共培养的内皮细胞迁移到血管床中并形成可灌注的血管。一种体外多步程序也能够制造厚的、血管化的心脏组织。基于细胞片的组织工程在制造3D心脏组织方面显示出巨大潜力,应该会有助于未来对严重心脏病的治疗以及人类组织模型的生产。