Stephen A E, Masiakos P T, Segev D L, Vacanti J P, Donahoe P K, MacLaughlin D T
Pediatric Surgical Research Laboratories, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3214-9. doi: 10.1073/pnas.051625998. Epub 2001 Feb 27.
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.
利用组织工程技术以及细胞与分子生物学方法，构建了一种可生物降解的支架，用于转染细胞以产生复杂蛋白质。苗勒管抑制物质（MIS）可导致哺乳动物胚胎中的苗勒管退化。MIS还能在体外使源自苗勒管结构的卵巢肿瘤细胞系和原发性卵巢癌细胞发生退化。为规避MIS复杂的纯化方案，将转染了人MIS基因的中国仓鼠卵巢细胞接种到聚乙醇酸纤维的可生物降解聚合物上，并证实了MIS的分泌。将聚合物 - 细胞移植物植入重度联合免疫缺陷小鼠的右侧卵巢蒂。随着时间的推移，小鼠血清中的MIS升高至超生理水平。在植入聚合物 - 细胞移植物一周后，将IGROV - 1人肿瘤植入左肾的肾包膜下。与对照组相比，在植入了产生MIS细胞的聚合物 - 细胞移植物的动物中，IGROV - 1肿瘤的生长受到显著抑制。这种新型的MIS递送系统可能对其他难以高效纯化的抑制剂有更广泛的应用，并为MIS在卵巢癌治疗中的作用提供了体内证据。
