Development of a Scaffold with Optimal Structure and Application to a Hybrid Artificial Liver for Chronic Liver Failure Patients

最佳结构支架的研制及其在慢性肝衰竭患者混合型人工肝中的应用

• 批准号: 15360443
• 负责人: KAJIWARA Toshihisa
• 金额: $ 6.66万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15360443/
• 关键词: Organoid; Scaffold; Hollow Fiber; Hepatocyte; Hyberid Artificial Liver; 多孔質担体; 多孔質体

1.Development of an elliptic hollow fiber as a novel scaffold for organoid formationWe have been developed a hybrid artificial liver by using a hepatocyte organoid, which has a tissue-like structure. One major problem in organoid culture is the depletion of oxygen at the core of an organoid. The survival thickness of such an organoid is limited by oxygen supply, because oxygen is transported by diffusion from the surface of an organoid. The optimum range of the thickness of an organoid is about 100 - 150μm. So we are trying to develop a scaffold to control the thickness of the organoid within suitable value. We designed an elliptic HF having less than 150μm minor diameter by using a simple annealing method. All hepatocytes were supplied with oxygen and formed an organoid without a dead cell layer in this hollow fiber. A hepatocyte organoid in an elliptic hollow fiber maintained ammonia removal activity twice as high as in the original hollow fiber for at least one month during culture. Albumin secretion activity of an organoid in an elliptic hollow fiber was also maintained for at least one month and was the same level as that of liver in a living body. These results indicate that an organoid culture by using an elliptic hollow fiber seems to be a promising technique to develop a hybrid artificial liver.2.Development of a hybrid artificial liver module with elliptic hollow fibersWe designed a hybrid artificial liver module with elliptic hollow fibers. Total volume of this module was 4.3 cm^3, and number of hollow fiber immobilized in the module was 336. Hepatocytes were immobilized in lumen of hollow fibers. Following this, the module was evaluated in perfusion culture. This novel module was maintained liver specific functions at high level for at least one month of culture. In conclusion, these organoid culture and module by using an elliptic HF seems to be a promising technique to develop a hybrid artificial liver.

1.椭圆形中空纤维作为类器官形成支架的研究利用肝细胞类器官，我们研制了一种具有组织样结构的混合型人工肝。类器官培养中的一个主要问题是类器官核心处的氧耗尽。这种类器官的存活厚度受到氧气供应的限制，因为氧气是通过从类器官表面扩散来运输的。类器官的最佳厚度范围约为100 - 150μm。因此，我们试图开发一种支架，以控制类器官的厚度在合适的值。我们用一种简单的退火方法设计了一个小直径小于150μm的椭圆形HF。所有肝细胞都被供应氧气，并在该中空纤维中形成没有死细胞层的类器官。在培养过程中，椭圆形中空纤维中的肝细胞类器官至少在一个月内保持两倍于原始中空纤维中的氨去除活性。椭圆形中空纤维中的类器官的白蛋白分泌活性也维持至少一个月，并且与活体中的肝脏的白蛋白分泌活性处于相同水平。这些结果表明，利用椭圆形中空纤维进行类器官培养是一种很有前途的技术，可以用于混合型人工肝的研制。2.椭圆形中空纤维混合型人工肝模块的研制设计了一种椭圆形中空纤维混合型人工肝模块。该组件的总体积为4.3 cm^3，固定在组件中的中空纤维的数量为336根。将肝细胞固定在中空纤维的内腔中。随后，在灌注培养中评估该模块。这种新的模块在至少一个月的培养中保持高水平的肝脏特异性功能。总之，这些类器官的培养和模块使用椭圆形HF似乎是一个有前途的技术，以开发一个混合型人工肝。

项目成果

異形断面中空糸を用いた肝細胞組織体(オルガノイド)培養法の開発

开发使用不规则截面中空纤维的肝细胞组织（类器官）培养方法

• 发表时间: 2004
• 期刊: 第41回化学関連支部合同九州大会講演予稿集
• 作者: J.Fukuda et al.;T.Kajiwara et al.;入江裕 他;蓮尾達也 他;J.Fukuda et al.;T.Kajiwara et al.;Y.Irie et al.;T.Hasuo et al.;J.Fukuda et al.;J.Fukuda et al.;T.Kajiwara et al.;蓮尾達也 他
• 通讯作者: 蓮尾達也 他

A.A.Ibrahim et al.: "The role for cell adhesion on formation of hepatocyte spheroid using stationary polyurethane form culture"The 16th Symposium on Chemical Engineering Daejeon/Chungnam-Kyushu and Cornerstone of International Collaboration for Chemical E

A.A.Ibrahim等人：“细胞粘附对使用固定聚氨酯形式培养物形成肝细胞球体的作用”第16届化学工程研讨会大田/忠南九州和化学E国际合作基石

繊維便覧(第4部門4・11・1節 人工肝臓)

纺织手册（第 4 部分第 4、11、1 人工肝）

• 发表时间: 2004
• 作者: Shigeru Naito;Munehiko Minoura;Munenobu Takeda;H. YOSHINO;福田淳二 他
• 通讯作者: 福田淳二 他

Hybrid artificial liver with polyurethane foam / shperoid culture for treatment of acute liver failure

聚氨酯泡沫/类球体培养混合人工肝治疗急性肝衰竭

• 发表时间: 2004
• 期刊: Proceedings of The 10th Asian Pacific Confederation of Chemical Engineering Congress (CD-ROM)
• 作者: Yugo Iwasaki;Tsuneo Yamane;T.Kajiwara et al.
• 通讯作者: T.Kajiwara et al.

The role for cell adhesion on formation of hepatocyte spheroid using stationary polyurethane foam culture

细胞粘附对固定聚氨酯泡沫培养肝细胞球体形成的作用

• 发表时间: 2003
• 期刊: Proceedings of The 16th Symposium on Chemical Engineering Daejeon/Chungnam -Kyushu and Cornerstone of International Collaboration for Chemical Engineering
• 作者: A.A.Ibrahim et al.