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1. 发明公开

EP1773978A2 PERFUSED THREE-DIMENSIONAL CELL/TISSUE DISEASE MODELS 有权转让
标题翻译：丰富的梦幻精灵ZELLEN- / GEWEBEERKRANKUNGSMODELLE
公开(公告)号：EP1773978A2
公开(公告)日：2007-04-18
申请号：EP05779763.1
申请日：2005-05-19
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , University of Pittsburgh of the Commonwealth System of Higher Education
发明人： DOMANSKY, Karel , GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , WELLS, Alan
IPC分类号： C12M1/34 , 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。主要特征是该系统可以在适合于药物开发中通常使用的机器人类型的高通量测定的多孔板格式中使用。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。

3. 发明授权

EP1064353B1 VASCULARIZED PERFUSED MICROTISSUE/MICRO-ORGAN ARRAYS 无效
标题翻译：密克罗尼西亚的VASKULARISIERTE PERFUNDIERTE ANORDNUNGENFÜRMIKROGEWEBE
公开(公告)号：EP1064353B1
公开(公告)日：2002-11-06
申请号：EP99913967.8
申请日：1999-03-18
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , POWERS, Mark, J. , DOMANSKY, Karel , THOMPSON, Charles, D.
IPC分类号： C12M3/04 , C12M1/34
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，其适用于将基质内的细胞接种和附着，并将种子细胞的形态发生转化为复杂的分层组织或器官结构，其中所述基质包括通道或血管，培养基，氧气或可以灌注其他营养液或体液，同时控制整个灌注路径中的营养物质和外源性代谢物的梯度，与灌注速率无关，和（2）用于检测基质内或细胞暴露的材料中任一细胞的变化的传感器装置，发达。制造微阵列的方法包括微加工，微胶印，压花，激光钻孔和电沉积加工。细胞可以是一种或多种，分化或未分化。在一个优选的实施方案中，用包含内皮细胞的细胞混合物接种基质，所述内皮细胞将通道形成“血管”，以及至少一种类型的实质细胞，例如肝细胞，胰腺细胞或其它器官细胞。该系统可用于筛选对细胞的影响的材料，用于细胞对材料的影响（例如，以等同于药物的组织代谢的方式），或用于测试必需的生物学上的材料首先感染细胞或组织，如病毒。该装置还可用于提供用于扩大干细胞的生理环境，或用于在体外实现基因治疗。

4. 发明公开

EP1064353A2 VASCULARIZED PERFUSED MICROTISSUE/MICRO-ORGAN ARRAYS 无效
标题翻译：血管灌注安排微结构和微器官
公开(公告)号：EP1064353A2
公开(公告)日：2001-01-03
申请号：EP99913967.8
申请日：1999-03-18
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , POWERS, Mark, J. , DOMANSKY, Karel , THOMPSON, Charles, D.
IPC分类号： C12M3/04 , C12M1/34
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.

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