Mini-mini-hearts | developing a medium-throughput engineered cardiac chamber platform using hpscs
Jana Hecking (TNW-BET)*, #, Mariel Cano Jorge (TNW-BET)*, José Manuel Rivera Arbeláez (TNW-BET & EEMCS-BIOS)*, Maureen Dannenberg (TNW-BET), Danique Snippert (TNW-BET), Simone Ten Den (TNW-BET), Robert Passier (TNW-BET)
*Equally contributing authors. # E-mail: j.hecking@student.utwente.nl
Abstract
Introduction: Engineered 3D cardiac models have emerged as tools to model human (patho-)physiology in vitro. Although advantageous, models such as organoids, heart-on-chips, and engineered-heart-tissues fail to mimic the fluid-pumping function of the heart. Researchers at Applied Stem Cell Technologies (AST) have overcome this limitation by introducing an engineered cardiac chamber known as ‘mini-heart’ which pumps fluid and can be used to measure ejection fraction. However, its fabrication suffers through complexity, low throughput, and the high number of cardiomyocytes required.
Objective: Towards a more versatile and standardized 3D cardiac model, we have developed the ‘mini-mini-heart platform’ (MH). A modular and versatile system with 50% fewer cells per cardiac chamber, compatible with a 12-well plate format.
Methods: The MH fabrication is a 3-step process: casting outer gelatin molds, inner gelatin molds and tissue formation. During the final step, a fibrin-gel containing human pluripotent stem cell derived cardiomyocytes and human cardiac fibroblasts is loaded into the cavity between the molds.
Results: We have now successfully fabricated MHs in a 12-well plate format. Preliminary results have shown that we can evaluate tissue compaction and cardiac performance during spontaneous beating and under electrical stimulation. MHs compacted 50% over the first 5 days and successfully followed 2 Hz pacing.
Discussion/Conclusion: Future steps will focus on quantifying hemodynamic metrics (ejection fraction) and expanding the platform’s applications for disease modeling. MHs will contribute towards the development of functional and scalable models, potentially transforming the landscape of drug testing and cardiac research.