Functional arrays of human pluripotent stem cell-derived cardiac microtissues.

Autor: Thavandiran N; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada., Hale C; Amgen Discovery Research, Amgen Inc., South San Francisco, CA, USA., Blit P; CCRM, Toronto, Ontario, Canada., Sandberg ML; A2 Biotherapeutics Inc., Agoura Hills, CA, USA., McElvain ME; A2 Biotherapeutics Inc., Agoura Hills, CA, USA., Gagliardi M; McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada., Sun B; McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada., Witty A; McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada., Graham G; CCRM, Toronto, Ontario, Canada., Do VTH; CCRM, Toronto, Ontario, Canada., Bakooshli MA; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada., Le H; Amgen Discovery Research, Amgen Inc., South San Francisco, CA, USA., Ostblom J; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada., McEwen S; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada., Chau E; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada., Prowse A; CCRM, Toronto, Ontario, Canada., Fernandes I; McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada., Norman A; CCRM, Toronto, Ontario, Canada., Gilbert PM; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.; Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada., Keller G; McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada., Tagari P; Amgen Discovery Research, Amgen Inc., South San Francisco, CA, USA., Xu H; A2 Biotherapeutics Inc., Agoura Hills, CA, USA. Hxu@a2biotherapeutics.com., Radisic M; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. m.radisic@utoronto.ca.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada. m.radisic@utoronto.ca.; Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada. m.radisic@utoronto.ca., Zandstra PW; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. peter.zandstra@ubc.ca.; CCRM, Toronto, Ontario, Canada. peter.zandstra@ubc.ca.; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada. peter.zandstra@ubc.ca.; Michael Smith Laboratories, School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada. peter.zandstra@ubc.ca.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Apr 24; Vol. 10 (1), pp. 6919. Date of Electronic Publication: 2020 Apr 24.
DOI: 10.1038/s41598-020-62955-3
Abstrakt: To accelerate the cardiac drug discovery pipeline, we set out to develop a platform that would be capable of quantifying tissue-level functions such as contractile force and be amenable to standard multiwell-plate manipulations. We report a 96-well-based array of 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues - termed Cardiac MicroRings (CaMiRi) - in custom 3D-print-molded multiwell plates capable of contractile force measurement. Within each well, two elastomeric microcantilevers are situated above a circumferential ramp. The wells are seeded with cell-laden collagen, which, in response to the gradual slope of the circumferential 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 the 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 the 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.
Databáze: MEDLINE
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