Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering
Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering
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DOI：
10.1016/j.jconrel.2014.12.016
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发表时间：
2015-05-10
影响因子：
10.8
通讯作者：
Okano, Teruo
中科院分区：
文献类型：
--
作者：
Sakaguchi, Katsuhisa;Shimizu, Tatsuya;Okano, Teruo
用预先分离的细胞构建三维组织是新药和药物发现研究的一项很有前途的成果。我们的实验室用一种创新和独特的方法构建了3D组织，用于对多个细胞片进行分层。与其他细胞输送方法相比，细胞片具有更高的细胞密度和更高的移植效率，因此保持了高效的再生功能。细胞片已经应用于再生医学治疗各种疾病的临床应用。因此，在我们开发更有效的细胞片治疗方法的过程中，我们正在通过对细胞片进行分层来构建3D组织。当地的动物组织和器官有大量的毛细血管来供应氧气和营养物质，并清除废物分子。在我们对血管化的心脏细胞膜的研究中，我们发现细胞膜内的内皮细胞自发地形成血管网络，就像体内的毛细血管一样。为了通过将多个细胞片分层来构建更厚的3D组织，在细胞片的血管网络内具有介质或血液流动是至关重要的。因此，为了在细胞片血管网络中灌流培养液或血液以维持所有细胞的活性，我们开发了两种类型的血管床：(1)基于股骨肌肉的血管床，(2)基于合成胶原凝胶的血管床。这两个血管床都成功地提供了关键的培养液流动，使12层细胞膜得以存活。这样的生物反应器系统与细胞板工程技术相结合，已经产生了功能丰富的血管3D组织。在这里，我们解释和讨论了通过适当连接细胞片和3D组织工程来获得血管网络的各种过程。(C)2014爱思唯尔B.V.保留所有权利。
Construction of three-dimensional (3D) tissues with pre-isolated cells is a promising achievement for novel medicine and drug-discovery research. Our laboratory constructs 3D tissues with an innovative and unique method for layering multiple cell sheets. Cell sheets maintain a high-efficiently regenerating function, because of the higher cell density and higher transplantation efficiency, compared to other cell-delivery methods. Cell sheets have already been applied in clinical applications for regenerative medicine in treating patients with various diseases. Therefore, in our search to develop a more efficient treatment with cell sheets, we are constructing 3D tissues by layering cell sheets. Native animal tissues and organs have an abundance of capillaries to supply oxygen and nutrients, and to remove waste molecules. In our investigation of vascularized cardiac cell sheets, we have found that endothelial cells within cell sheets spontaneously form blood vessel networks as in vivo capillaries. To construct even thicker 3D tissues by layering multiple cell sheets, it is critical to have a medium or blood flow within the vascular networks of the cell sheets. Therefore, to perfuse medium or blood in the cell sheet vascular network to maintain the viability of all cells, we developed two types of vascular beds; (1) a femoral muscle-based vascular bed, and (2) a synthetic collagen gel-based vascular bed. Both vascular beds successfully provide the critical flow of culture medium, which allows 12-layer cell sheets to survive. Such bioreactor systems, when combined with cell sheet engineering techniques, have produced functional vascularized 3D tissues. Here we explain and discuss the various processes to obtain vascular networks by properly connecting cell sheets and the engineering of 3D tissues. (C) 2014 Elsevier B.V. All rights reserved.