Advisor(s)
Jianyi (Jay) Zhang
Committee Member(s)
Jack M Rogers
Gregory P Walcott
Hanyu Zhang
Lei Ye
Matthew W Kay
Document Type
Dissertation
Date of Award
1-1-2025
Degree Name by School
Doctor of Philosophy (PhD) School of Engineering
Abstract
The adult mammalian heart lacks regenerative capacity to replenish cardiomyocytes (CMs) lost due to myocardial infarction (MI). Instead, the damaged heart undergoes extensive remodeling that significantly impairs normal cardiac function and may eventually lead to heart failure. Recent therapies that implant engineered tissues fabricated from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have shown promising results with improved cardiac function and structural integration. However, the extent of electrophysiological coupling between engineered and host tissue remains unclear. This is a critical factor for functional integration of the implant as well as for arrhythmia risk arising from the implant. Our study aims to investigate electrophysiological coupling between implanted tissue grafts and the host myocardium using an in-vivo pig model. We implanted engineered hiPSC-CMs spheroids into the pig’s heart and allowed them to integrate for 1 week. We then imaged organotypic cardiac tissue slices harvested from the implant zone to assess electrical coupling. We demonstrated for the first time that the engineered cardiac spheroids we implanted into swine hearts electrically coupled, enabling the host myocardium to drive the graft at a high heart rate up to 240 beats per minute (4 Hz). Further, we demonstrated the potential for mechanisms involving re-entry and graft automaticity to cause graft-associated arrhythmogenicity during transplantation. We also developed a novel “all-optical” system incorporating optogenetics and cardiac optical mapping that is particularly well-suited for studying bidirectional electrical coupling in engineered tissue transplantation. This study may have significant implications for cell transplantation therapies.
ProQuest Publication Number
ISBN
9798315792505
Recommended Citation
Guragain, Bijay, "Electrophysiological Integration Of Engineered Tissue Graft With The Host Swine Myocardium" (2025). All ETDs from UAB. 6842.
https://digitalcommons.library.uab.edu/etd-collection/6842
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