Tissue-engineered cells producing complex recombinant proteins inhibit ovarian cancer in vivo.
Techniques of tissue engineering and cell and molecular biology were used to create a biodegradable scaffold for transfected cells to produce complex proteins. Mullerian Inhibiting Substance (MIS) causes regression of Mullerian ducts in the mammalian embryo. MIS also causes regression in vitro of ovarian tumor cell lines and primary cells from ovarian carcinomas, which derive from Mullerian structures. In a strategy to circumvent the complicated purification protocols for MIS, Chinese hamster ovary cells transfected with the human MIS gene were seeded onto biodegradable polymers of polyglycolic acid fibers and secretion of MIS confirmed. The polymer-cell graft was implanted into the right ovarian pedicle of severe combined immunodeficient mice. Serum MIS in the mice rose to supraphysiologic levels over time. One week 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 graft of MIS-producing cells, compared with controls. This novel MIS delivery system could have broader applications for other inhibitory agents not amenable to efficient purification and provides in vivo evidence for a role of MIS in the treatment of ovarian cancer.
Pediatric Surgical Research Laboratories, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
A E
AE
Stephen
P T
PT
Masiakos
D L
DL
Segev
J P
JP
Vacanti
P K
PK
Donahoe
D T
DT
MacLaughlin
D000818:Animals; D054304:Anti-Mullerian Hormone; D016466:CHO Cells; D017690:Cell Transplantation / Q000379:methods*; D006224:Cricetinae; D005260:Female; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D013735:Testicular Hormones / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D006131:Growth Inhibitors; D011993:Recombinant Fusion Proteins; D013735:Testicular Hormones; D054304:Anti-Mullerian Hormone