Open multi-culture platform for simple and flexible study of multi-cell type interactions

Abstract

The study of multi-cell-type (MCT) interactions has the potential to significantly impact our understanding of tissue and disease biology. Such studies require innovative culture tools for unraveling the contributions of each cell type. Micro- and macro-scale platforms for MCT culture each have different advantages and disadvantages owing to their widely different capabilities, availability, and ease-of-use. However, as evidenced in the literature, there are very few examples of MCT studies and culture platforms, suggesting both biological and technical barriers. We have developed an open multi-culture platform to promote more rapid progress by integrating advantages of both micro- and macro-scale culture devices. The proposed open multi-culture platform addresses technical barriers by allowing easy customization, independent control of basic physical culture parameters, and incorporation of multiple culture modalities (e.g., 2D, 3D, transwell, and spheroid). The design also permits the user to obtain independent endpoints for each culture region. We demonstrate use of the platform in two example studies where we evaluated how cell ratio and cell types influence the response of triple negative breast cancer cells to heat damage and Hedgehog signaling. We also show that the platform can improve soluble factor transport between cell types compared to compartmentalized macro- and micro-scale alternatives. Last, we examine current and future challenges of the platform. We envision simple, yet flexible and customizable, platforms such as this will be important for advancing in vitro study of tissue and tumor biology.