Abstract 305: An innovative 3D porous scaffold-based perfusion bioreactor system for the in vitro maintenance and expansion of primary breast cancer tissue

Abstract

Abstract Introduction: Development of cancer treatment protocols has traditionally been based on studies in experimental animal models or taking advantage of human established tumor cell lines for in vitro and in vivo assays. Here we present an innovative method to culture breast cancer tissues in porous 3D scaffolds by using a perfusion-based bioreactor system. Experimental procedures: Freshly excised estrogen-receptor positive breast cancer specimens were fragmented and cultured in a 3D “sandwich-like format” between porous scaffolds under perfusion flow, with “on-line” monitoring of environmental condition. DMEM/F12, supplemented with 10% autologous human serum, was used as a culture medium in the presence or absence of estrogens. The ability of tumor cells to survive and expand into the scaffold in perfusion culture as well as their ability to recapitulate features of the original breast cancer specimens was histologically assessed. Results: With this innovative method we were able to preserve viability and to promote the expansion of breast cancer cells from surgical specimens together with accompanying stromal and immune cells into the porous scaffold. Expanding cancer cells were viable after 21 days and recapitulating the initial histology with formation of glands. Administration of estrogen to the culture medium was associated with increased expansion of cancer cells into the scaffold starting at 14 days of culture. Conclusions: Culture of breast cancer tissue in a 3D scaffold-based bioreactor preserves malignant, interstitial and immunocompetent cells present in surgically excised breast cancer samples, thus allowing direct testing of basic cancer research hypotheses in intact, complex human tumor microenvironments. Furthermore, it might allow a direct evaluation of the effects of various treatments on malignant and non-transformed cells. This engineered in vitro model could be extended beyond the context of our primary scientific interest, namely breast cancer, as a broader platform allowing animal-free testing of innovative approaches for the treatment of human malignancies, possibly in the direction of personalized medicine. Citation Format: Manuele G. Muraro, Simone Muenst, Giulio C. Spagnoli, Daniel Oertli, Walter P. Weber, Savas D. Soysal. An innovative 3D porous scaffold-based perfusion bioreactor system for the in vitro maintenance and expansion of primary breast cancer tissue. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 305. doi:10.1158/1538-7445.AM2015-305