A tissue engineering approach for liver tissue organization in vitro

体外肝组织组织的组织工程方法

• 批准号: 12650784
• 负责人: KAMIHIRA Masamichi
• 金额: $ 2.56万
• 依托单位: NAGOYA UniVersity
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12650784/
• 关键词: Tissue engineering; Artificial matrix; Bioartificial liver; Hepatocyte spheroid; Cytochrome P-450; RhoA; HGF; テイッシュエンジニアリング; 肝臓; 肝実質細胞; 組織再生; 自己組織化; スフェロイド; 人工臓器; 組織培養

We previously described the mass preparation ofhepatocyte spheroids in a cell suspension. Addition ofa synthetic polymer, Eudragit S 100 (a co-polymer of methacrylic acid and methylmethacrylate), to the culture medium as an artificial matrix has been found to promote cell aggregation and induce spheroid formation. The present study examines co-cultures of hepatocytgs and liver non-parenchymal cells to further enhance the stable expression of liver functions. Hetero-spheroids consisting of "hepatocyteT.and non-parenchymal cells were also formed by adding the polymer to the culture medium. The expression levels of liver functions depended on the mixing ratio of the cells The values ofalbumin secretion, anmlonia removal and urea synthesis were the highest when equal number ofhepatocytes and non-parenchymal cells were mixed. The hetero-spherpids maintained a higher level ofalbumin secretion for over 4 weeks^compared with co-cultured cells without the polymer and spheroids consisting of hepatocytes solely.^Other liver functions such as anunonia removal and cytochrome P-450 activity in'hetero-spheroid cultures were also maintained at a high level throughout the 4-week culture period.

我们之前描述了在细胞悬浮液中大量制备肝细胞球体。研究发现，在培养基中加入合成聚合物Eudragit S 100(甲基丙烯酸和甲基丙烯酸甲酯的共聚物)作为人工基质，可以促进细胞聚集和诱导球体的形成。本研究探讨肝细胞与肝非实质细胞的共培养，以进一步增强肝功能的稳定表达。在培养液中加入聚合物也可形成由“肝细胞T”和非实质细胞组成的异质球体。肝功能的表达水平取决于细胞的混合比例。当相同数量的肝细胞和非实质细胞混合时，白蛋白分泌、线粒去除和尿素合成的数值最高。与没有聚合物和仅由肝细胞组成的共培养细胞相比，异质球体保持了较高的白蛋白分泌水平。在整个4周的培养过程中，异质球体的其他肝功能，如无核细胞清除和细胞色素P-450活性也保持在较高水平。

项目成果

K.Yamada,M.Kamihira,S.Iijima: "Self-organization of liver constitutive cells mediated by artificial matrix and improvement of liver functions in long-term culture"Biochemical Engineering Journal. 7(印刷中). (2001)

K. Yamada、M. Kamihira、S. Iijima：“人工基质介导的肝脏组成细胞的自组织和长期培养中肝脏功能的改善”《生物化学工程杂志》7（出版中）。

Keisuke Yamada, Masamichi Kamihira and Shinji lijima ;: "Self-organization of liver constitutive cells mediated by artificial matrix and improvement of liver functions in long-term culture"Biochemical Engineering Journal,. 8. 135-143 (2001)

Keisuke Yamada、Masamichi Kamihira 和 Shinji lijima ；：“人工基质介导的肝脏组成细胞的自组织和长期培养中肝功能的改善”《生物化学工程杂志》，。

Yamada, K., Kamihira, M., Iijima, S.: "Self-organization of liver constitutive cells mediated by artificial matrix and improvement of liver functions in long-term culture"Biochemical Engineering Journal. 8(2). 135-143 (2001)

Yamada, K.、Kamihira, M.、Iijima, S.：“人工基质介导的肝脏组成细胞的自组织和长期培养中肝功能的改善”生物化学工程杂志。