In this recent scientific result, our team demonstrates that the in vivo-like dynamic environment provided by the MIVO® device allows for better modeling of the 3D tumor environment and predicting drug efficacy in vivo compared to a static in vitro model.
In this work, 3D SKOV-3 cell-laden alginate hydrogels were established as ovarian tumor models and cultured within a fluid-dynamic bioreactor (MIVO®) device able to mimic the capillary flow dynamics feeding the tumor. Cisplatin efficacy tests were performed within the device over time and compared with (i) the in vitro culture under static conditions and (ii) a xenograft mouse model with SKOV-3 cells, by monitoring and measuring cell proliferation or tumor regression, respectively, over time.
After one week of treatment with 10 µM cisplatin, viability of cells within the 3D hydrogels cultured under static conditions remained above 80%. In contrast, the viability of cells within the 3D hydrogels cultured within dynamic MIVO® decreased by up to 50%, and very few proliferating Ki67-positive cells were observed through immunostaining. Analysis of drug diffusion, confirmed by computational analysis, explained that these results are due to different cisplatin diffusion mechanisms in the two culture conditions. Interestingly, the outcome of the drug efficacy test in the xenograft model was about 44% of tumor regression after 5 weeks, as predicted in a shorter time just in the fluid-dynamic in vitro tests carried out within MIVO® device.
A. Marrella, G. Varani, M. Aiello, I. Vaccari, C. Vitale, M. Mojzisek, C. Degrassi and S. Scaglione, (2020) “3D fluid-dynamic ovarian cancer model resembling systemic drug administration for efficacy assay”, ALTEX – Alternatives to animal experimentation.