Development of the hepatic toxicity evaluation test using a mini-bioartificial liver and ^<13>C stability isotope compounds

使用微型生物人工肝和^ 13 C稳定性同位素化合物开发肝毒性评价试验

• 批准号: 17590476
• 负责人: MATSUURA Tomokazu
• 金额: $ 2.24万
• 依托单位: JIKEI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590476/
• 关键词: toxic evaluation test; bioartificial organ; substitute organ; stability isotope; breath test; glucose metabolism; cancer; 3 dimensional cell culture; バイオ人工肝臓; ^<13>C

The xinobiotic evaluation method used by human cells is a technique to fill metabolic differences between Homo sapiens and experimental animals. However, conventional single-layered culture method cannot reproduce the functions of cell in the body. We can use the bioartificial organs which we made by three-dimensional high density culture method as a substitute organ of human tissue and organs. In the present study, we performed development of the metabolic and toxic test using ^<13>C stability isotope compounds for sensitive metabolic evaluation in a substitute organ.Three-dimensional culture in a bioreactor is a large-scaled culture compared to single-layered culture. Therefore it is difficult to operate a lot of reactors. On this account a system to carefully judge the operation situation of one reactor is necessary. At first we made a mixed gas feeder to maintain simply three-dimensional culture system, without a CO_2 incubator and a large-scaled controller, supplied oxygen of cult … More ure system. I also developed the metabolism discharge ^<13>CO_2 assay method using a ^<13>C stability isotope labeled compound to perform toxic evaluation and a certain specific metabolism evaluation on culture course. The advantages of this method are ; 1)We can evaluate a specific metabolism by using a specific labeled compound, 2)We can easily get samples as exhaust gas from a reservoir, and do not need to open a reactor, and 3) We can easily measure ^<13>CO_2 for only 2'30" by a infrared spectrophotometer.As a result of this study, we developed the metabolic and toxic evaluation system for performing metabolic simulation in the body using bioartificial organs and ^<13>C stability isotope labeled compounds. Objective evaluation will apply metabolism modeling and computer simulation. Before animal and clinical examinations, the substitute analysis using bioartificial organs and a stability isotope labeled compounds will become useful for evaluation of the toxicity/metabolism of quality of drugs and foods in future. Less

人类细胞使用的异生生物评估方法是一种填补智人和实验动物之间代谢差异的技术。然而，传统的单层培养方法不能复制体内细胞的功能。我们可以用三维高密度培养方法制成的生物人工器官作为人体组织器官的替代器官。在本研究中，我们进行了代谢和毒性试验的发展，使用~(13)C稳定性同位素化合物在替代器官中进行敏感的代谢评价。与单层培养相比，生物反应器中的三维培养是一种大规模的培养。因此，操作许多反应堆是困难的。为此，有必要建立一个系统来仔细判断一个反应堆的运行情况。首先，我们制作了一个混合气体供给器，以维持简单的三维培养系统，没有CO_2培养箱和大型控制器，为CULT…提供氧气更可靠的系统。建立了代谢释放量测定方法，利用稳定性同位素标记化合物对培养过程进行了毒性评价和特定的代谢评价。这种方法的优点是：1)我们可以利用特定的标记化合物来评估特定的代谢；2)我们可以很容易地从储气罐中获得废气样本，而不需要打开反应堆；3)我们可以很容易地用红外光谱仪测量2‘30“的^&lt；13&gt；CO_2。作为这项研究的结果，我们开发了利用生物人工器官和^&lt；13&gt；C稳定性同位素标记化合物进行体内代谢模拟的代谢和毒性评价系统。客观评价将应用新陈代谢建模和计算机模拟。在动物和临床检验之前，利用生物人工器官和稳定同位素标记化合物的替代分析将成为未来评估药物和食品质量的毒性/代谢的有用方法。较少

项目成果

The hepatic sinusoidal endothelial lining and colorectal liver metastasis

肝窦内皮层与结直肠肝转移

• 发表时间: 2007
• 期刊: World J Gastroenterol 13
• 作者: Braet F;Saito M;Matsuura T;et. al.
• 通讯作者: et. al.

Bioreactors for 3-dimensional high density culture of human cells

用于人体细胞三维高密度培养的生物反应器

• 发表时间: 2006
• 期刊: Human Cell (In press)
• 作者: Saito M;Matsuura T;Masaki M;Maehashi H;Shimizu K;Hatabe Y;Iwahori T;Suzuki T;Bract F;Mtsuura T
• 通讯作者: Mtsuura T

Reconstruction of liver organoid using a bioreactor

• DOI: 10.3748/wjg.v12.i12.1881
• 发表时间: 2006-03-28
• 期刊: WORLD JOURNAL OF GASTROENTEROLOGY
• 影响因子: 4.3
• 作者: Saito, Masaya;Matsuura, Tomokazu;Braet, Filip
• 通讯作者: Braet, Filip

ガス混合装置及びガス混合法

气体混合设备及气体混合方法

• 发表时间: 2006

Bioreactors for 3-dimensional high-density culture of human cells.

用于人体细胞三维高密度培养的生物反应器。

• 发表时间: 2006
• 期刊: Human Cell 19
• 作者: Masayoshi Abe;Hiroshi Hama;Takayuki Shirakusa;Akinori Iwasaki;Nobuhumi Ono;Nobuhiro Kimura;Tony E Hugli;Noriko Okada;Takeshi Katsuragi;Hidechika Okada;Matsuura T
• 通讯作者: Matsuura T