Tissue-engineered cells producing complex recombinant proteins inhibit ovarian cancer in vivo

Techniques of tissue engineering and cell and molecular biology were used t o create a biodegradable scaffold for transfected cells to produce complex proteins. Mullerian Inhibiting Substance (MIS) causes regression of Mulleri an ducts in the mammalian embryo. MIS also causes regression in vitro of ov arian tumor cell lines and primary cells from ovarian carcinomas, which der ive from Mullerian structures. In a strategy to circumvent the complicated purification protocols for MIS, Chinese hamster ovary cells transfected wit h the human MIS gene were seeded onto biodegradable polymers of polyglycoli c acid fibers and secretion of MIS confirmed. The polymer-cell graft was im planted into the right ovarian pedicle of severe combined immunodeficient m ice. Serum MIS in the mice rose to supraphysiologic levels over time. One w eek after implantation of the polymer-cell graft, IGROV-1 human tumors were implanted under the renal capsule of the left kidney. Growth of the IGROV- 1 tumors was significantly inhibited in the animals with a polymer-cell gra ft of MIS-producing cells, compared with centrols. This novel MIS delivery system could have broader applications for other inhibitory agents not amen able to efficient purification and provides in vivo evidence for a role of MIS in the treatment of ovarian cancer.