Abstract 18251: Establishment of an in vitro Platform, the Hydrogel Mattress, to Enhance Maturation and Evaluate Contractile Function of Individual hiPSC-CMs
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have great potential as tools for cell based therapy, disease modeling and drug discovery. However, their contractile properties have not been routinely evaluated; as methods to do so are cumbersome and not easily translated to standard laboratories. We sought to develop a more efficient protocol to evaluate hiPSC-CM mechanical properties, at the single cell level. Individual hiPSC-CMs were cultured on a hydrogel based platform, termed the hydrogel mattress, and their cellular contractile properties were evaluated using video based edge detection (Figure A). We found individual hiPSC-CMs maintained for 5 days on the mattress assumed an elongated shape (Figure B) and exhibited robust, reproducible cell shortening (~10% versus <1% for standard culture). We further found hiPSC-CM cellular contraction and peak cell shortening amplitude was comparable to that of freshly isolated adult rabbit and mouse ventricular CMs (Figure C). In addition, hiPSC-CMs maintained on the mattress exhibited characteristics of mature CMs including action potential waveform, calcium handling and pharmacological response to myofilament calcium sensitizers. We further show a positive correlation with the established traction force microscopy method. We demonstrate the hydrogel mattress platform enables routine characterization and quantification of contractile performance of isolated hiPSC-CMs. This platform can be extended to in vitro disease modeling, drug discovery and drug induced cardiotoxicity testing. Further, the mattress can be easily adapted to virtually any laboratory, thus streamlining cellular mechanical evaluation of individual hiPSC-CMs in vitro.
Author Disclosures: T.K. Feaster: None. C.H. Williams: None. L. Wang: None. A.G. Cadar: None. Y.W. Chun: None. C.C. Lim: None. B.C. Knollmann: None. C.C. Hong: None.
- © 2015 by American Heart Association, Inc.