Real-Time Force and Frequency Analysis of Engineered Human Heart Tissue Derived from Induced Pluripotent Stem Cells Using Magnetic Sensing

Tissue Eng Part C Methods. 2016 Oct;22(10):932-940. doi: 10.1089/ten.TEC.2016.0257. Epub 2016 Sep 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Arrhythmia Agents / pharmacology
  • Biosensing Techniques / methods*
  • Cardiotonic Agents / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Isoproterenol / pharmacology
  • Magnetic Fields*
  • Mechanical Phenomena
  • Myocardial Contraction / drug effects*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology*
  • Tissue Engineering / methods*
  • Verapamil / pharmacology

Substances

  • Anti-Arrhythmia Agents
  • Cardiotonic Agents
  • Verapamil
  • Isoproterenol