The assessment of cancer metastatic potential and InSphero's Akura™ Immune Flow platform
Evaluation of novel therapeutics often fails to reliably predict severe complications in patients, especially when circulating cells are involved. The reasons may include inter-species differences upon using animal models or the lack of relevant in vitro systems. Current in vitro systems mainly rely on static investigations of different cell types, leading to an overestimation of effects originating from non-representative cell-tissue interactions. The incorporation of medium flow facilitates mimicking physiological conditions more closely.
To tackle the current limitations of perfused organ-on-chip approaches, we developed a microfluidic chip and operation concept, which prevents undesired sedimentation and accumulation of cells in suspensions. The Akura™ Immune Flow platform was designed to study flow-dependent recruitment of circulating cells to different tissue spheroids via gravity-driven perfusion over several days. Moreover, the platform features standardized formats for co-culturing up to seven spheroids with suspended cells in each microfluidic channel. On-chip staining protocols enable monitoring of the co-culture. The system allows for the application and extraction of cellular components and liquid for further off-chip analyses.
As an application, we used the Akura™ Immune Flow Platform to study metastatic invasion of prostate cancer (PCa ) cell into different human healthy microtissues, such as liver and bone. Primary 3D human liver microtissues and bone-mineralized microtissues of MG63 cells were co-cultured under optimized medium conditions in the Akura™ Immune Flow Chip. Both tissue types could be retained in the respective chambers and remained viable over 14 days under similar medium conditions. Loading different PCa cell lines into the chip, containing 3 bone and 4 liver microtissues, led to the attachment of the cancer cells to the microtissues. The system offers the potential to identify tumor cells and tissue factors that determine cell invasion into healthy tissues, which may guide metastasis-target drug development.
The simple design of the chip using gravity-driven perfusion facilitates user-friendly operation and high-throughput implementation in cancer research and drug testing. The selected applications demonstrate the relevance of using flow configurations for physiologically more complex processes. This work constitutes an important step towards device application in basic research as well as for efficacy studies of immunotherapy drug candidates.
Download the poster about the assessment of cancer metastatic potential in Akura™ Immune Flow platform
