DEVELOPMENT OF SUPER-BIOARTIFICIAL LIVER BASED ON THE HEPATOCYTE-SPECIFIC POLYMER DESIGN AND GENETIC ENGINEERING

基于肝细胞特异性聚合物设计和基因工程的超级生物人工肝的开发

• 批准号: 06403035
• 负责人: AKAIKE Toshihiro
• 金额: $ 10.05万
• 依托单位: TOKYO INSTITUTE OF TECHNOLOGY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06403035/
• 关键词: Super-bioartificial liver; asialoglycoprotein model; super-hepatocyte; gene transfection; biomimetics; hepatocyte; extracellular matrix; スーパー人工肝臓; アシアロ糖タンパク質モデル; 細胞増殖性; 細胞移動性; 高分子ミセル; ハイブリッド人工肝臓; β-ガラクトース; バイオ人工肝臓; Fアクチン; PVLA; 細胞移動; リポフ

This research project aimed at the development of super-bioartificial liver which is based on the cell biology, genetic engineering and polymer chemistry. The main approaches are as follows :1 Design and syntheses of asialoglycoprotein model polymer(PVLA)were successfully made to regulate the cell attachment, morphology, differentiation and proliferation of hepatocytes. The clarification of the machanism regulating the cellular phonomena was made based on the AFM and QCM analysis of polymer coated surface.2 Cell-specific gene-transfection was successfully made to hepatocytes cultured on PVLA with use of Lipofection method.3 Development of hepatocyte proliferation by control of cyrokine network of TNF-alpha was made for bioartificial liver.4 Clarification of the development of Liver cells community was done focused on the analysis of terminal differentiation of Kupffer cells from bone marrow cells

本课题以细胞生物学、基因工程和聚合物化学为基础，致力于超生物人工肝的研制。主要研究内容如下：1设计合成了可调节肝细胞贴壁、形态、分化和增殖的去唾液酸糖蛋白模型聚合物(PVLA)。通过对聚合物涂层表面的AFM和QCM分析，阐明了细胞膜的调控机制。2.利用脂质体转染法成功地对PVLA上培养的肝细胞进行了细胞特异性基因转导。3.生物人工肝应用肿瘤坏死因子-α环化网络调控肝细胞增殖的进展。4.阐明了肝细胞群落的发育，重点分析了Kupffer细胞向骨髓细胞的终末分化。

项目成果

大河原久子.宮崎純一.苅部幸代.佐藤純彦.寺岡 慧.中川芳彦.広谷紗千子.太田和夫.赤池敏宏: "Diffusion chamber型人工膵島 における免疫隔離膜としての高分子膜の孔径の評価" 人工臓器. (25)「4」. 794-797 (1996)

Hisako Okawara、Junichi Miyazaki、Yukiyo Karibe、Sumihiko Sato、Kei Teraoka、Yoshihiko Nakakawa、Sachiko Hirotani、Kazuo Ota、Toshihiro Akaike：“扩散室型人工胰岛中作为免疫隔离膜的聚合物膜的孔径评估”人工器官。 25）“4”。794-797（1996）。

H.OHGAWARA,J.MIYAZAKI,S.KARIBE,N.KATAGIRI F.TASHIRO,T.AKAIKE: "Assessment of pore size of a semipemeable membrane for immunoisolation on xenoimplantation of pancreatic B cell using a diffusion chamber." Transplantation proceedings.(27)「6」. 3319-3320 (1996

H.OHGAWARA、J.MIYAZAKI、S.KARIBE、N.KATAGIRI F.TASHIRO、T.AKAIKE：“使用扩散室评估用于胰腺 B 细胞异种移植免疫隔离的半透膜孔径。” 27）“6”3319-3320（1996）。

Chong-su CHO, Akira KOBAYASHI, Mitsuaki GOTO, Keung-Hong PARK, Toshihiro AKAIKE: "Difference in Adhesion and Proliferation of Fibroblast between Langmuir-Blodgett Films and Cast Surfaces of Poly(g-benzy 1 L-glutamate)/Poly(enthylene oxide)diblock copolyme

Chong-su CHO、Akira KOBAYASHI、Mitsuaki GOTO、Keung-Hong PARK、Toshihiro AKAIKE：“Langmuir-Blodgett 薄膜与聚（g-benzy 1 L-谷氨酸）/聚（乙烯）铸件表面之间成纤维细胞粘附和增殖的差异

Chong-Su CHO, Mitsuaki GOTO, Akira KOBAYASHI, Kazuhiko KOBAYASHI Toshihiro AKAIKE: "Effect of ligand orientation on hepatocyte attachment onto the poly (N-p-vinylbenzyl-o-β-D-guluconamide) as amodel ligand of asialoglicoprotein" J. biomater. Sci. Polym. e

Chong-Su CHO、Mitsuaki GOTO、Akira KOBAYASHI、Kazuhiko KOBAYASHI Toshihiro AKAIKE：“配体方向对肝细胞附着在作为去唾液酸糖蛋白模型配体的聚（N-对乙烯基苄基-o-β-D-葡萄糖酰胺）上的影响”J. biomater。科学。

M.MORITA et al: "Infammatory cytokines upregulate the ICAM-1 expression on primary cultured mouse hepatocytes and T cell adhesion" Hepatology. 19. 426-431 (1994)

M.MORITA 等人：“炎症细胞因子上调原代培养小鼠肝细胞上的 ICAM-1 表达和 T 细胞粘附”肝病学。