Micro-nano scale mass transfer in the reconstructed hepatocyte structure

重建肝细胞结构中的微纳尺度传质

• 批准号: 20246041
• 负责人: TANISHITA Kazuo
• 金额: $ 31.12万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20246041/
• 关键词: バイオ人工肝臓; 幹細胞; 物質移動; 胆管; 毛細胆管; 毛細血管; 共培養; 星細胞; 力学的刺激; 3次元組織構築; 内皮細胞; 多重層化

Three-dimensional (3D) culture of hepatocytes is essential in order to reconstruct functional hepatic tissues in vitro. We have established the 3D stacked-up culture, a 3D culture method for the reconstruction of layered hepatocyte tissues which mimic the structure of hepatic cords. Hepatic stellate cells (HSCs) form a functional unit with endothelia and hepatocytes in the liver to play a pivotal role in heterotypic cellular communication. We confirmed that HSCs mediated the communication between hepatocytes and ECs in terms of EC morphogenesis. This tri-culture model allows us to investigate the roles of HSC_s as both facilitators and integrators of cell. cell communication between hepatocytes and ECs, and is useful for investigating heterotypic cellular communication in vitro. We also developed a 3D stacked-up culture for SHs based on a degradation of microporous poly (D, L-lactide-co-glycolide acids) (PLGA) membranes with defined geometry. The 3D stack-up culture based on the degradation of microporous PLGA membranes will enable reconstruction of multilayered hepatic tissues with highly differentiated functions in vitro. Finally we achieved the vascularization into the 3D reconstructed structure of hepatocyte by micro-fluidic device. Thereby the technology of reconstructed liver tissue has been advanced to the final application to the bio-artificial liver.

肝细胞的三维培养是体外重建功能性肝组织的必要条件。我们建立了一种模拟肝索结构的分层肝细胞组织的三维培养方法--三维叠层培养法。肝星状细胞（hepatic stellate cells，HSC）是肝脏中与内皮细胞和肝细胞共同组成的功能单位，在异型细胞通讯中起着关键作用。我们证实，HSC介导的EC之间的交流EC形态发生。这一三元培养模型使我们能够研究HSC作为细胞的促进者和整合者的作用。在肝细胞和EC之间的细胞通讯，并用于研究异型细胞通讯在体外。我们还开发了一种三维堆叠培养SH的基础上降解的微孔聚（D，L-丙交酯-共-乙交酯酸）（PLGA）膜与定义的几何形状。基于微孔PLGA膜降解的三维堆叠培养将能够在体外重建具有高度分化功能的多层肝组织。最后利用微流控装置实现了肝细胞血管化的三维重建。从而将肝组织重建技术推进到生物人工肝的最终应用。

项目成果

The reconstructed tube formation by integrated cellular structure

通过集成细胞结构重建管状结构

• 发表时间: 2009
• 作者: 須藤亮;et al.
• 通讯作者: et al.

Effect of hypoxia on formation of three-dimensional microvessel networks by endothelial cells in vitro

缺氧对体外内皮细胞三维微血管网络形成的影响

• 发表时间: 2008
• 期刊: Journal of Biomechanical Science and Engineering 3
• 作者: Tanishita;K.;et al.
• 通讯作者: et al.

Spatio-temporal control of hepatic stellate cell-endothelial cell interactions for reconstruction of vascularized liver constructs in vitro

肝星状细胞-内皮细胞相互作用的时空控制用于体外重建血管化肝脏结构

• 发表时间: 2011
• 作者: Sudo;R.;Tanishita;K.;et al
• 通讯作者: et al

マイクロ流路デバイスにおける肝細胞組織-血管ネットワーク間相互作用の定量評価

微流体装置中肝细胞组织-血管网络相互作用的定量评估

• 发表时间: 2011
• 作者: 須藤亮、谷下一夫;ほか
• 通讯作者: ほか

PLGA membrane sandwich culture model of biliary epithelial cells for reconstruction of bile duct

PLGA膜夹心胆道上皮细胞培养模型用于胆管重建

• 发表时间: 2010
• 作者: 松尾薫;他
• 通讯作者: 他