IMPROVED BIOARTIFICAL LIVER FUNCTION IN HEPATIC FAILURE

改善肝衰竭患者的生物人工肝功能

• 批准号: 6177328
• 负责人: RORY P REMMEL
• 金额: $ 20.58万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6177328
• 关键词: bioreactors; biotransformation; cell cell interaction; cell differentiation; cytochrome P450; disease /disorder model; dogs; extracellular matrix; integrins; liver cells; liver failure; liver function; tissue /cell culture; tissue engineering

DESCRIPTION: (Adapted from the applicant's abstract) This application proposes to develop a bioartificial liver (BAL) to be used as a bridging device to liver transplantation or for spontaneous recovery for patients with acute liver failure. The problems with the currently developed BAL are that the liver cells lose important synthetic and biotransformation functions. Preliminary work from the laboratory suggests that cell/cell and cell/matrix interactions are important for hepatocyte differentiation and function. The hypothesis of the grant is that by understanding and manipulating adhesion receptors involved in cell/matrix and cell/cell interactions that hepatocyte differentiation and biotransformation can be improved, and therefore improve the efficacy of a BAL. The Specific Aims are: 1. To demonstrate that adhesion receptor interactions between rat or porcine hepatocytes and the culture substratum or other liver cells regulate biotransformation functions; 2. Drug induction of P450 is matrix dependent and will enhance the biotransformation capacity of the BAL; 3. To demonstrate that an optimized BAL consisting of matrix entrapped hepatocyte spheroids pretreated with a combination of P450 inducers will provide superior therapeutic efficacy in a canine liver failure model.

描述：（改编自申请人摘要）本申请

项目成果

Primary hepatocytes outperform Hep G2 cells as the source of biotransformation functions in a bioartificial liver.

• 发表时间: 1994-07
• 期刊: Annals of surgery
• 影响因子: 9
• 作者: S. Nyberg;R. Remmel;H. Mann;M. Peshwa;Wei-Shou Hu;F. Cerra

Mechanistics of formation and ultrastructural evaluation of hepatocyte spheroids.

肝细胞球体的形成机制和超微结构评估。

• DOI: 10.1007/bf02722946
• 发表时间: 1996
• 期刊: In vitro cellular & developmental biology. Animal
• 作者: Peshwa,MV;Wu,FJ;Sharp,HL;Cerra,FB;Hu,WS
• 通讯作者: Hu,WS

Induction of the metabolism of midazolam by rifampin in cultured porcine hepatocytes: preliminary evidence for CYP3A isoforms in pigs.

利福平在培养的猪肝细胞中诱导咪达唑仑的代谢：猪体内 CYP3A 亚型的初步证据。

• 发表时间: 1999
• 期刊: Drug metabolism and disposition: the biological fate of chemicals.
• 作者: Hosagrahara,VP;Hansen,LK;Remmel,RP
• 通讯作者: Remmel,RP

Effects of hepatocyte growth factor on viability and biotransformation functions of hepatocytes in gel entrapped and monolayer culture.

肝细胞生长因子对凝胶包埋和单层培养中肝细胞活力和生物转化功能的影响。

• DOI: 10.1097/00003246-199507000-00014
• 发表时间: 1995
• 期刊: Critical care medicine
• 影响因子: 8.8
• 作者: Hu,MY;Cipolle,M;Sielaff,T;Lovdahl,MJ;Mann,HJ;Remmel,RP;Cerra,FB
• 通讯作者: Cerra,FB

Blunt injury augments interleukin-6 but not tumor necrosis factor in isolated, perfused rat hindlimbs.

在离体、灌注的大鼠后肢中，钝性损伤会增强白细胞介素 6，但不会增强肿瘤坏死因子。

• DOI: 10.1097/00005373-199407000-00016
• 发表时间: 1994
• 期刊: The Journal of trauma
• 作者: Cipolle,MD;Pasquale,MD;Shearer,J;Caldwell,M;Cerra,F
• 通讯作者: Cerra,F