Chronic optical pacing conditioning of h-iPSC engineered cardiac tissues
Year: 2019
Type: article
Abstract: The immaturity of human induced pluripotent stem cell derived engineered cardiac tissues limits their ability to regenerate damaged myocardium and to serve as robust in vitro models for human disease and drug toxicity studies. Several chronic biomimetic conditioning protocols, including mechanical stretch, perfusion, and/or electrical stimulation promote engineered cardiac tissue maturation but have significant technical limitations. Non-contacting chronic optical stimulation using heterologously expressed channelrhodopsin light-gated ion channels, termed optogenetics, may be an advantageous alternative to chronic invasive electrical stimulation for engineered cardiac tissue conditioning. We designed proof-of-principle experiments to successfully transfect human induced pluripotent stem cell derived engineered cardiac tissues with a desensitization resistant, chimeric channelrhodopsin protein, and then optically paced engineered cardiac tissues to accelerate maturation. We transfected human induced pluripotent stem cell engineered cardiac tissues using an adeno-associated virus packaged chimeric channelrhodopsin and then verified optically paced by whole cell patch clamp. Engineered cardiac tissues were then chronically optically paced above their intrinsic beat rates in vitro from day 7 to 14. Chronically optically paced resulted in improved engineered cardiac tissue electrophysiological properties and subtle changes in the expression of some cardiac relevant genes, though active force generation and histology were unchanged. These results validate the feasibility of a novel chronically optically paced paradigm to explore non-invasive and scalable optically paced–induced engineered cardiac tissue maturation strategies.
Source: Journal of Tissue Engineering
Institutions: University of Louisville, Kosair Charities, Cardiovascular Innovation Institute, National Institutes of Health, National Heart, Lung, and Blood Institute, Kyoto University, Center for iPS Cell Research and Application, Kyoto University, RIKEN, RIKEN Center for Biosystems Dynamics Research
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,000
Awards: Research of disease modeling and drug discovery through the maturation regulation of human iPS cell-derived cardiac tissue recapitulating human heart function, Development of cardiomyopathy-specific iPS cell-derived 3-dimensional biomaterial-based cardiac tissues suitable for drug discovery, G3891949333, Research for the identification of biomarkers regarding the progression of cardiomyopathy based on imaging mass spectrometry and the therapeutic approach, Development of a method of functional integration between host and graft on the transplantation therapy of human iPS cell-derived cardiac tissues, Development of self-growing vascular graft using decellularized vascular tissue and human iPS cell-derived vascular cells, G7749180837, Development of efficient organ protection during deep hypothermic circulatory arrest based on "artificial hibernation"
OpenAlex ID: W2937014246