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.TM.,
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.