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1. 发明申请

WO2005123950A3 PERFUSED THREE-DIMENSIONAL CELL/TISSUE DISEASE MODELS 审中-公开
标题翻译：丰富的三维细胞/组织疾病模型
公开(公告)号：WO2005123950A3
公开(公告)日：2006-04-13
申请号：PCT/US2005017594
申请日：2005-05-19
申请人： MASSACHUSETTS INST TECHNOLOGY , UNIV PITTSBURGH , DOMANSKY KAREL , GRIFFITH LINDA G , TANNENBAUM STEVEN R , WELLS ALAN
发明人： DOMANSKY KAREL , GRIFFITH LINDA G , TANNENBAUM STEVEN R , WELLS ALAN
IPC分类号： B01L3/00 , C12M1/00 , C12M1/32 , C12M1/34 , C12Q1/68 , C12M1/12 , C12M1/22
CPC分类号： B01L3/502715 , B01J2219/00315 , B01J2219/00743 , B01L3/50255 , B01L3/50273 , B01L3/502738 , B01L2300/0681 , B01L2300/0829 , B01L2300/0861 , B01L2400/0481 , B01L2400/0638 , B33Y80/00 , C12M23/12 , C12M23/40 , C12M25/14 , C12M29/10
摘要： A system has been constructed that recapitulate the features of a capillary bed through normal human tissue. The system facilitates perfusion of three-dimensional (3D) cell monocultures and heterotypic cell co-cultures at the length scale of the capillary bed. A major feature is that the system can be utilized within a "multiwell plate" format amenable to highthroughput assays compatible with the type of robotics commonly used in pharmaceutical development. The system provides a means to conduct assays for toxicology and metabolism and as a model for human diseases such as hepatic diseases, including hepatitis, exposure-related pathologies, and cancer. Cancer applications include primary liver cancer as well as metastases. The system can also be used as a means of testing gene therapy approaches for treating disease and inborn genetic defects.
摘要翻译：已经构建了通过正常人体组织重现毛细血管床特征的系统。该系统便于在毛细血管床的长度尺度上灌注三维（3D）细胞单一培养物和异型细胞共培养物。一个主要特征是该系统可以在“多孔板”格式中使用，适合与通常用于制药开发的机器人类型兼容的高通量测定。该系统提供了进行毒理学和代谢测定的手段，并且作为人类疾病（如肝脏疾病，包括肝炎，暴露相关病理和癌症）的模型。癌症应用包括原发性肝癌以及转移瘤。该系统也可用作检测基因治疗方法以治疗疾病和先天性遗传缺陷的手段。

2. 发明申请

WO2004011622A3 METHODS FOR PERFUSION AND PLATING OF PRIMARY HEPATOCYTES AND A MEDIUM THEREFORE 审中-公开
标题翻译：用于灌注和沉积原发性肝细胞的方法及其中间体
公开(公告)号：WO2004011622A3
公开(公告)日：2004-08-26
申请号：PCT/US0323869
申请日：2003-07-30
申请人： MASSACHUSETTS INST TECHNOLOGY , LEACH JOHN K , TANNENBAUM STEVEN R
发明人： LEACH JOHN K , TANNENBAUM STEVEN R
IPC分类号： C12N5/071 , G01N33/50 , C12N5/06 , C12N5/08
CPC分类号： G01N33/5005 , C12N5/067 , C12N2500/38 , C12N2501/999 , C12N2503/00
摘要： The present invention provides methods for culturing primary hepatocytes with improved long term function and improved viability, by plating the hepatocytes in the presence of an anti-oxidants) as well as an agent(s) which is a functional inhibitor of enzymes that generate reactive oxygen and reactive nitrogen species. One preferred embodiment provides a combination of 2-oxo-thizolidine and tocopherol succinate. Another preferred embodiment provides a combination of N methylarginine and mannitol.
摘要翻译：本发明提供了通过在抗氧化剂存在下电镀肝细胞来培养具有改善的长期功能和改善的存活力的原代肝细胞的方法）以及作为产生活性氧的酶的功能性抑制剂的药剂和活性氮物种。一个优选的实施方案提供2-氧代 - 噻唑烷和琥珀酸生育酚的组合。另一个优选实施方案提供了N，N-二甲基精氨酸和甘露糖醇的组合。

3. 发明申请

WO9947922A3 VASCULARIZED PERFUSED MICROTISSUE/MICRO-ORGAN ARRAYS 审中-公开
标题翻译：加压渗透微量/微生物阵列
公开(公告)号：WO9947922A3
公开(公告)日：1999-11-04
申请号：PCT/US9905974
申请日：1999-03-18
申请人： MASSACHUSETTS INST TECHNOLOGY
发明人： GRIFFITH LINDA G , TANNENBAUM STEVEN R , POWERS MARK J , DOMANSKY KAREL , THOMPSON CHARLES D
IPC分类号： B01J19/00 , C12M1/34 , C12M3/04 , C40B60/14 , G01N33/50
CPC分类号： G01N33/5038 , B01J19/0046 , B01J2219/00286 , B01J2219/00308 , B01J2219/00313 , B01J2219/00317 , B01J2219/00319 , B01J2219/00351 , B01J2219/00376 , B01J2219/00416 , B01J2219/00585 , B01J2219/00659 , B01J2219/0072 , B33Y10/00 , B33Y80/00 , B82Y30/00 , C12M21/08 , C12M23/12 , C12M41/46 , C40B60/14 , G01N33/5008 , G01N33/502 , G01N33/5058 , G01N33/5064 , G01N33/5073
摘要： Systems including (1) a micromatrix and perfusion assembly suitable for seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures, wherein the matrix includes channels or vessels through which culture medium, oxygen, or other nutrient or body fluids can be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of perfusion rate, and (2) sensor means for detecting changes in either cells within the matrix or in materials exposed to the cells, have been developed. Methods for making the micromatrices include micromachining, micromolding, embossing, laser drilling, and electro deposition machining. Cells can be of one or more types, either differentiated or undifferentiated. In a preferred embodiment, the matrix is seeded with a mixture of cells including endothelial cells which will line the channels to form "blood vessels", and at least one type of parenchymal cells, such as hepatocytes, pancreatic cells, or other organ cells. The system can be used to screen materials for an effect on the cells, for an effect of the cells on the materials (for example, in a manner equivalent to tissue metabolism of a drug), or to test a material on a biological that must first infect cells or tissues, such as viruses. The apparatus also can be used to provide a physiological environment for expansion of stem cells, or for enabling gene therapy in vitro.
摘要翻译：系统包括（1）微阵列和灌注组件，适合于将基质内的细胞接种和附着以及将接种细胞形态发生成复杂的分层组织或器官结构，其中基质包括培养基，氧或其他营养物质或体液可灌注，同时独立于灌注速率而在整个灌注路径中控制营养素和外源性代谢物的梯度，和（2）用于检测基质内或暴露于细胞的物质中细胞变化的传感器装置发达。制造微基体的方法包括微加工，微成型，压花，激光钻孔和电沉积加工。细胞可以是一种或多种类型，分化的或未分化的。在一个优选的实施方案中，将基质与细胞混合物接种，所述细胞混合物包括将使通道形成“血管”的内皮细胞，以及至少一种实质细胞，例如肝细胞，胰腺细胞或其他器官细胞。该系统可用于筛选材料对细胞的影响，细胞对材料的影响（例如，以等同于药物组织代谢的方式），或测试生物体上的材料首先感染细胞或组织，如病毒。该设备也可用于提供干细胞扩增的生理环境，或用于体外基因治疗。

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