Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells
Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells
复制标题
周细胞样血管周围细胞稳定的连续毛细血管网络的构建
DOI：
10.1089/ten.tea.2018.0186
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发表时间：
2019
影响因子：
4.1
通讯作者：
Ryo Sudo
中科院分区：
文献类型：
--
作者：
Kyoko Yamamoto;Kohei Tanimura;Masafumi Watanabe;Hiromu Sano;Hiroyuki Uwamori;Yo Mabuchi;Yumi Matsuzaki;Seok Chung;Roger D. Kamm;Kazuo Tanishita;Ryo Sudo
构建细小且连续的毛细血管网络是三维组织工程发展的一个基本挑战。特别是，为了构建成熟和稳定的毛细血管网络，重要的是考虑内皮细胞和周细胞之间的相互作用。本研究旨在构建由周细胞样血管周围细胞覆盖的稳定的毛细血管网络，以维持与体内毛细血管结构相似的小直径管腔。在微流控装置中，利用含有人脐静脉内皮细胞(HUVECs)和间充质干细胞(MSCs)的三维血管生成模型，研究了血管的萌发、毛细血管的伸展和稳定。测试了一系列HUVEC：MSC的比例，发现该比例是构建毛细血管结构的一个重要因素。我们发现，在HUVEC：MSC比例为1：1的情况下，可以构建稳定的、被MSC来源的血管周围细胞覆盖的毛细血管网络。所构建的毛细血管网络具有直径<lt；10-μm的连续管腔，可保持至少21天。这一血管生成过程和基底膜的形成受HUVEC-MSC相互作用的调控。然而，如何构建稳定的毛细血管网络，使其保持与体内毛细血管结构相似的管腔大小(即直径10 μm)，目前还不清楚。在这项研究中，我们通过优化血管内皮细胞和血管周围细胞之间的相互作用，利用Anin体外三维血管生成模型，证明了稳定的毛细血管网络被周细胞样血管周围细胞覆盖。我们的3D血管生成模型可以在3D组织工程构建的血管形成的背景下与3D上皮细胞的3D培养相结合。
Construction of small and continuous capillary networks is a fundamental challenge for the development of three-dimensional (3D) tissue engineering. In particular, to construct mature and stable capillary networks, it is important to consider interactions between endothelial cells and pericytes. This study aimed to construct stable capillary networks covered by pericyte-like perivascular cells, which maintain the lumen of small diameter similar to that of capillary structuresin vivo. Vascular sprouting, capillary extension, and stabilization were investigated using a 3D angiogenesis model containing human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) in a microfluidic device. A series of HUVEC:MSC ratios was tested; the ratio was found to be an important factor in the construction of capillary structures. We found that stable capillary networks that were covered by MSC-derived perivascular cells can be constructed at 1:1 HUVEC:MSC ratio. The constructed capillary networks had continuous lumens with <10-μm diameter, which were maintained for at least 21 days. This angiogenic process and basement membrane formation were regulated by HUVEC–MSC interactions.Impact StatementConstruction of capillary networks is a fundamental challenge for the development of three-dimensional (3D) tissue engineering. However, it is not well understood how to construct stable capillary networks that maintain a luminal size similar to that of capillary structuresin vivo(i.e., <10 μm diameter). In this study, we demonstrated the construction of stable capillary networks covered by pericyte-like perivascular cells using anin vitro3D angiogenesis model by optimizing interactions between endothelial cells and perivascular cells. Our 3D angiogenesis model can be combined with 3D culture of epithelial cells in the context of vascularization of 3D tissue-engineered constructs.