PT  - JOURNAL ARTICLE
AU  - Thavandiran, Nimalan
AU  - Hale, Christopher
AU  - Blit, Patrick
AU  - Sandberg, Mark L.
AU  - McElvain, Michele E.
AU  - Gagliardi, Mark
AU  - Sun, Bo
AU  - Witty, Alec
AU  - Graham, George
AU  - Mcintosh, May
AU  - Bakooshli, Mohsen A.
AU  - Le, Hon
AU  - Ostblom, Joel
AU  - McEwen, Samuel
AU  - Chau, Erik
AU  - Prowse, Andrew
AU  - Fernandes, Ian
AU  - Gilbert, Penney M.
AU  - Keller, Gordon
AU  - Tagari, Philip
AU  - Xu, Han
AU  - Radisic, Milica
AU  - Zandstra, Peter W.
AU  - Nojima, Dana
AU  - Vargas, Hugo
AU  - Qu, Yusheng
AU  - Motani, Alykhan
AU  - Reagan, Jeff
TI  - Functional arrays of human pluripotent stem cell-derived cardiac microtissues
AID  - 10.1101/566059
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 566059
4099  - http://biorxiv.org/content/early/2019/03/05/566059.short
4100  - http://biorxiv.org/content/early/2019/03/05/566059.full
AB  - To accelerate the cardiac drug discovery pipeline, we set out to develop a platform that would be amenable to standard multiwell-plate manipulations and be capable of quantifying tissue-level functions such as contractile force. We report a 96-well-based array of 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues - termed Cardiac MicroRings (CaMiRi) - in custom printed multiwell plates capable of contractile force measurement. Within each well, two elastomeric microcantilevers are situated above a ramp. The wells are seeded with cell-laden collagen which, in response to the slope of the ramp, self-organizes around tip-gated microcantilevers to form contracting CaMiRi. The contractile force exerted by the CaMiRi is measured and calculated using the deflection of the cantilevers. Platform responses were robust and comparable across wells and we used it to determine an optimal tissue formulation. We validated contractile force response of CaMiRi using selected cardiotropic compounds with known effects. Additionally, we developed automated protocols for CaMiRi seeding, image acquisition, and analysis to enable measurement of contractile force with increased throughput. The unique tissue fabrication properties of the platform, and the consequent effects on tissue function, were demonstrated upon adding hPSC-derived epicardial cells to the system. This platform represents an open-source contractile force screening system useful for drug screening and tissue engineering applications.