Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US7078032

Title:Delivery of therapeutic biologicals from implantable tissue matrices
Inventors:MacLaughlin, David T.; Saugus, MA, USA
Vacanti, Joseph P.; Winchester, MA, USA
Donahoe, Patricia K.; Boston, MA, USA
Masiakos, Peter T.; Boston, MA, USA
Summary:This invention describes a system of implanting a cell-matrix structure with attached cells that stably express a gene encoding a biological modifier. Disclosed herein is method by which normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic proteins that are normally produced in small amounts, such as MIS or other members of the TGF-beta family, Herceptin, interferons, and anti-angiogenic factors. Further described are means by which such cells may be engineered to include a lethal gene prior to implantation into a matrix, such that the implanted cells may be destroyed once treatment is completed. A variety of implantation matrices are described, including those that are biodegradable over a period of time equal to or less than the expected period of treatment, during which the cells engraft to form a functional tissue producing the desired biologically active agent. The authors describe ectopic and orthotopic implantations, as well as matrices that may be formed of synthetic or natural materials and by chemical coupling at the time of implantation, using standard techniques for the formation of fibrous matrices from polymeric fibers. Micromachining and microfabrication techniques are described, as are methods by which micromolded substrates with polymeric hydrogels are involved in the parenteral delivery of such recombinant proteins. Further described are applications of such minimally invasive implantation strategies in the treatment of disorders characterized by excessive proliferation of tissue, such as with specific adinocarcinomas.
Abstract:Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, and anti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and/or active forms using conventional methods of purification, for the treatment of a variety of conditions.
US Patent Website:Click Here for Full Text of Patent
Title Number:US7078032
Application Number:US2003000690077
Date Filed:21/10/2003
Date Published:18/07/2006
Assignee:The General Hospital Corporation, Boston, MA, USA


 
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