Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Committee Co-Chair (if applicable)
stem cell; optogenetics; tissue engineering
The immaturity of engineered cardiac tissues (ECTs) limits their ability to regenerate damaged myocardium and to serve as in vitro disease models and surrogates for drug toxicity testing. Several chronic biomimetic conditioning protocols, including mechanical stretch, perfusion, and electrical stimulation promote ECT maturation but have significant technical limitations. Non-contacting chronic light stimulation using heterologously expressed light-sensitive ChIEF ion channels, termed optogenetics, may be an advantageous alternative to chronic electrical stimulation. As a proof of principle, we transfected ECTs using an AAV packaged ChIEF and then verified acute optical pacing (OP) by patch clamp. We then chronically OP ECTs for 7 days above the intrinsic beat rate. Chronic OP resulted in improved ECT electrophysiological properties; however, ECT force generation and histology remained unchanged. Some changes in cardiac relevant gene expression were noted. This work validates a novel chronic OP paradigm that can be used to identify strategies for optimal in vitro ECT maturation.
Dwenger, Marc M., "Maturation of human induced pluripotent stem cell derived engineered cardiac tissues using chief transfection and chronic optical pacing." (2018). Electronic Theses and Dissertations. Paper 2910.