Stem Cell Related Patent Number US7078032

Delivery of therapeutic biologicals from implantable tissue matrices

MacLaughlin, David T.; Saugus, MA, United States of America
Vacanti, Joseph P.; Winchester, MA, United States of America Donahoe, Patricia K.; Boston, MA, United States of America
Masiakos, Peter T.; Boston, MA, United States of America

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.

Application Number: US2003000690077

Date Filed: 10/21/03

Dated Published: 07/18/06

Assignee: The General Hospital Corporation, Boston, MA, United States of America