Three-dimensional constructs induce high cellular activity: Structural stability and the specific production of proteins and cytokines
Three-dimensional constructs induce high cellular activity: Structural stability and the specific production of proteins and cytokines
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DOI：
10.1016/j.bbrc.2010.10.007
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发表时间：
2010-11-05
影响因子：
3.1
通讯作者：
Akashi, Mitsuru
中科院分区：
文献类型：
--
作者：
Kadowaki, Koji;Matsusaki, Michiya;Akashi, Mitsuru
评估了由三维(3D)细胞结构诱导的稳定性和功能的特定性质，并与单层结构进行了比较。采用分层细胞操作技术构建了人成纤维细胞(FCS)和人脐血管内皮细胞(ECs)三维细胞多层膜。有趣的是，ECs均匀地附着在四层(4L)FCS上，在厘米尺度上广泛观察到紧密连接的形成，而在单层(1L)FCS上观察到不均匀的EC结构域结构。研究细胞结构产生热休克蛋白70(Hsp70)和白介素6(IL-6)的情况，以阐明三维结构对细胞功能的影响。与EC单层相比，内皮细胞在4L-Fc结构上黏附后Hsp70的表达降低。令人惊讶的是，通过三维结构的形成，Hsp70对热休克的产生响应比非热休克显著增加了大约10倍，而单层结构没有变化。此外，炎症细胞因子IL-6的产生随着FCS层数的增加而显著减少。据我们所知，这是关于3D结构对细胞稳定性和功能的基本影响的第一份报告。这些发现不仅对组织工程学很重要，而且对基础细胞生物学也很重要。(C)2010 Elsevier Inc.保留所有权利。
The specific properties responsible for the stability and function induced by three-dimensional (3D) cellular constructs were evaluated and compared to a monolayer structure. 3D-cellular multilayers composed of human fibroblast cells (FCs) and human umbilical vascular endothelial cells (ECs) were fabricated by a hierarchical cell manipulation technique. Interestingly, the ECs adhered homogeneously onto four-layered (4L) FCs, and tight-junction formation was widely observed at the centimeter scale, while heterogeneous EC domain structures were observed on the monolayered (1L) FCs. The production of heat shock protein70 (Hsp70) and interleukin-6 (IL-6) from the cellular structures were investigated to elucidate any 3D-structural effect on cellular function. The Hsp70 expression of the ECs decreased after adhesion onto the 4L-FC structure as compared with the EC monolayer. Surprisingly, the Hsp70 production response to heat shock increased drastically by approximately 10-fold as compared with a non-heat shock by 3D structure formation, whereas the monolayer structures showed no change. Moreover, the production of the inflammatory cytokine IL-6 decreased significantly depending on the layer number of FCs. To the best of our knowledge, this is the first report on a basic, 3D-structural effect on cellular stability and function. These findings could be important for not only tissue engineering, but also for basic cell biology. (C) 2010 Elsevier Inc. All rights reserved.