Real-Time Force and Frequency Analysis of Engineered Human Heart Tissue Derived from Induced Pluripotent Stem Cells Using Magnetic Sensing.
Engineered heart tissues made from human pluripotent stem cell-derived cardiomyocytes have been used for modeling cardiac pathologies, screening new therapeutics, and providing replacement cardiac tissue. Current methods measure the functional performance of engineered heart tissue by their twitch force and beating frequency, typically obtained by optical measurements. In this article, we describe a novel method for assessing twitch force and beating frequency of engineered heart tissue using magnetic field sensing, which enables multiple tissues to be measured simultaneously. The tissues are formed as thin structures suspended between two silicone posts, where one post is rigid and another is flexible and contains an embedded magnet. When the tissue contracts it causes the flexible post to bend in proportion to its twitch force. We measured the bending of the post using giant magnetoresistive (GMR) sensors located underneath a 24-well plate containing the tissues. We validated the accuracy of the readings from the GMR sensors against optical measurements. We demonstrated the utility and sensitivity of our approach by testing the effects of three concentrations of isoproterenol and verapamil on twitch force and beating frequency in real-time, parallel experiments. This system should be scalable beyond the 24-well format, enabling greater automation in assessing the contractile function of cardiomyocytes in a tissue-engineered environment.
1 Department of Mechanical Engineering, University of Washington , Seattle, Washington.|2 Center for Cardiovascular Biology, University of Washington , Seattle, Washington.|3 Institute for Stem Cell and Regenerative Medicine, University of Washington , Seattle, Washington.
Kevin S
KS
Bielawski
1 Department of Mechanical Engineering, University of Washington , Seattle, Washington.|2 Center for Cardiovascular Biology, University of Washington , Seattle, Washington.|3 Institute for Stem Cell and Regenerative Medicine, University of Washington , Seattle, Washington.
Andrea
A
Leonard
2 Center for Cardiovascular Biology, University of Washington , Seattle, Washington.|3 Institute for Stem Cell and Regenerative Medicine, University of Washington , Seattle, Washington.|4 Department of Bioengineering, University of Washington , Seattle, Washington.
Shiv
S
Bhandari
2 Center for Cardiovascular Biology, University of Washington , Seattle, Washington.|3 Institute for Stem Cell and Regenerative Medicine, University of Washington , Seattle, Washington.|4 Department of Bioengineering, University of Washington , Seattle, Washington.|5 Department of Pathology, University of Washington , Seattle, Washington.|6 Department of Medicine/Cardiology, University of Washington , Seattle, Washington.
Chuck E
CE
Murry
1 Department of Mechanical Engineering, University of Washington , Seattle, Washington.|2 Center for Cardiovascular Biology, University of Washington , Seattle, Washington.|3 Institute for Stem Cell and Regenerative Medicine, University of Washington , Seattle, Washington.|4 Department of Bioengineering, University of Washington , Seattle, Washington.
Nathan J
NJ
Sniadecki
D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D015374:Biosensing Techniques / Q000379:methods*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007545:Isoproterenol / Q000494:pharmacology; D060526:Magnetic Fields; D055595:Mechanical Phenomena; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D014700:Verapamil; D007545:Isoproterenol