Date on Master's Thesis/Doctoral Dissertation
5-2018
Document Type
Master's Thesis
Degree Name
M.S.
Department
Pharmacology and Toxicology
Degree Program
Pharmacology and Toxicology, MS
Committee Chair
Keller, Bradley
Committee Co-Chair (if applicable)
Guido, William
Committee Member
Guido, William
Committee Member
Cai, Lu
Committee Member
Beverly, Levi
Committee Member
Hood, Joshua
Author's Keywords
stem cell; optogenetics; tissue engineering
Abstract
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.
Recommended Citation
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.
https://doi.org/10.18297/etd/2910