Heart failure (HF) represents an enormous clinical problem that imposes a significant burden both to society and survivors. During a myocardial infarction, cardiomyocytes are damaged due to a lack of oxygen to the left ventricle and as a result these cells die. The dead cells are then replaced by fibrotic scar tissue that inhibits the heart from properly pumping blood to the rest of the heart. The current treatments of HF do not reverse the damage that the left ventricle experiences and as a result many people experience recurrent heart failure and sometime cardiac arrest. The field of cellular reprogramming investigates the process of direct reprogramming of endogenous cardiac fibroblasts to cardiomyocytes as a novel approach to help the heart to pump blood properly after a myocardial infarction. In this project, we used a biodegradable hyaluronic acid (HA) hydrogel to encapsulate Adeno-associated virus (AAV) 9 engineered to deliver the reporter gene green fluorescent protein (GFP) or five transcription factors (G: Gata4, M: Mef2c, T: Tbx5, M: Mesp1and M: Myocardin) in pigs' heart post-myocardial. Our method represents a unique approach to transfect cardiomyocyte cells in vivo post-myocardial infarct in pig. This study also demonstrates a cardiac functional improvement with the injection of hydrogel gel, AAV9, and selected transcription factors in the compromised area of the left ventricle. This novel method reduced the scar tissue in the compromised area of the heart compared to control.
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Details
Title
Novel therapeutic intervention for myocardial infarction in large animal model
Creators
Maria Mercedes - DU
Contributors
Andres Kriete (Advisor) - Drexel University (1970-)
Awarding Institution
Drexel University
Degree Awarded
Master of Science (M.S.)
Publisher
Drexel University; Philadelphia, Pennsylvania
Number of pages
34 pages
Resource Type
Thesis
Language
English
Academic Unit
School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University