Development of the liver lobule-type culture device

肝小叶型培养装置的研制

• 批准号: 24659591
• 负责人: MITAKA Toshihiro
• 金额: $ 2.33万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659591/
• 关键词: 小型肝細胞; 胆管上皮細胞; デバイス; シリコーン; 細胞外基質; 毛細胆管; 組織形成; 内皮細胞; 血管内皮細胞; 人工肝臓; スキャフォールド; 共培養; マイクロ流体; シリコーンゴム; 基底膜

We have developed devices made of silicon for the co-culture of rat small hepatocytes (SHs) and biliary epithelial cells (BECs). Cells could proliferate and survive on a silicon-device that oxygen freely passes through. We coated channels of the silicon-device with various ECM to examine their effects on morphogenesis. However, we have not found an optimal condition for that bile ducts (BDs) reconstructed by BECs connect to bile canaliculi of hepatic organoids reconstructed by matured SHs. By using microfluidic platform, we analyzed angiogenesis in 3D cultures in which collagen gel separated rat mature hepatocytes and endothelial cells (ECs), and found that ECs formed vascular sprouts in collagen gels. Laminins 111 and 521 were necessary for hepatic progenitor cells to differentiate into BECs and to form mature duct structures, respectively. A transcription factor Grhl2 enhanced the morphogenesis of BDs by regulating the expression and the location of claudins 3 and 4.

我们已经开发出由硅制成的装置，用于大鼠小肝细胞（SH）和胆管上皮细胞（BEC）的共培养。细胞可以在氧气自由通过的硅装置上增殖和存活。我们用各种ECM涂覆硅装置的通道以检查它们对形态发生的影响。然而，我们还没有找到一个最佳的条件，胆管（BD）重建的胆管（BD）连接到肝细胞重建成熟的肝类器官的胆小管。我们利用微流控平台分析了胶原凝胶分离大鼠成熟肝细胞和内皮细胞（EC）的三维培养中的血管生成，发现EC在胶原凝胶中形成血管芽。层粘连蛋白111和521分别是肝祖细胞分化为BEC和形成成熟导管结构所必需的。转录因子Grhl2通过调节claudins 3和4的表达和位置来增强BD的形态发生。

项目成果

シンポジウムI「マウス正常及び障害肝での肝細胞供給システムの解明」

研讨会一“阐明正常和受损小鼠肝脏中的肝细胞供应系统”

• 发表时间: 2012
• 作者: 谷水直樹;三高俊広
• 通讯作者: 三高俊広

転写因子Grainylhead like-2による上皮細胞の形態形成及び分化可塑性の制御

转录因子Grainylhead like-2对上皮细胞形态发生和分化可塑性的调节

• 作者: 谷水直樹;三高俊広
• 通讯作者: 三高俊広

胆管上皮細胞の時空間的なHeterogeneity

胆管上皮细胞的时空异质性

• 发表时间: 2014
• 作者: 谷水直樹;西川祐司;三高俊広
• 通讯作者: 三高俊広

The stabilization effect of mesenchymal stem cells on the formation of microvascular networks in a microfluidic device

间充质干细胞对微流控装置中微血管网络形成的稳定作用

• 发表时间: 2013
• 期刊: Journal of Biomechanical Science and Engineering
• 作者: Kyoko Yamamoto;Kohei Tanimura;Yo Mabuchi;Yumi Matsuzaki;Seok Chung;Roger D. Kamm;Mariko Ikeda;Kazuo Tanishita;Ryo Sudo.
• 通讯作者: Ryo Sudo.

Three-dimensional liver cancer cell migration assay under interstitial flow in amicrofluidic system

微流控系统间质流下三维肝癌细胞迁移实验

• 发表时间: 2012
• 作者: Kawai T;Noguchi H;Kuise T;Nakatsuka A;Katayama A;Imagawa N;Kataoka HU;Saitoh I;Noguchi Y;Watanabe M;Fujiwara T.;宮崎安弘;瀧口修司;須藤亮
• 通讯作者: 須藤亮