Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6197575

Title:Vascularized perfused microtissue/micro-organ arrays
Inventors:Griffith, Linda G.; Cambridge, MA, USA
Tannenbaum, Steven; Framingham, MA, USA
Powers, Mark J.; Cambridge, MA, USA
Domansky, Karel; Cambridge, MA, USA
Thompson, Charles D.; Cambridge, MA, USA
Summary:Described herein is a novel apparatus comprised of microtissue/micro-organ arrays, methods and uses thereof. The invention relates to a system comprised of a micromatrix and perfusion assembly suitable for the seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures. Further disclosed are properties of the matrix including channels or vessels through which the culture medium, oxygen, or other nutrient or body fluids may be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of the perfusion rate. Also provided is a sensor for detecting changes in either cells within the matrix or in materials exposed to the cells. Methods of constructing the micromatrices are disclosed, as are methods of seeding with a mixture of cells including endothelial cells in order to form blood vessels along the channels, and at least one type of parenchymal cell such as hepatocytes or pancreatic cells. Multiple embodiments of the invention are provided, as are multiple applications which include the use of such an apparatus in assaying compounds for their effects on cells and the effects of cells on the compounds.
Abstract: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.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6197575
Application Number:US1999000272227
Date Filed:18/03/1999
Date Published:06/03/2001
Assignee:Massachusetts Institute of Technology, Cambridge, MA, USA


 
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