Brown University

Cardiac Differentiation Potential is Modulated by Genetic Background: Implications for Personalized Medicine

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Abstract:
Cardiovascular diseases are some of the most common and most lethal diseases in the world. On top of that, the only treatment option available that would allow for cardiovascular function to be restored to healthy levels long-term is a heart transplant. Not only are heart transplants difficult to come by – the waiting list is almost double the number of hearts available each year – but even this solution may require life-long immunosuppressant and drug use. By instead using regenerative medicine and tissue engineering, it is possible to create innovative solutions using human induced pluripotent stem cell derived cardiomyocytes that may create a pathway towards restoring functionality to damaged hearts. Furthermore, these cardiomyocytes can be used to perform extensive cardiotoxicity testing in human cells, providing a more accurate and appropriate medium for assessing the implications of new drugs heading to market, as well as how a patient’s heart may react to a prescribed drug regimen. Currently, one of the largest barriers to these fields of research is the large number of pure cardiomyocytes that must be produced to meet the demands of academia and industry. This is the motivation behind the work presented here, which aims to optimize the cardiomyocyte differentiation process of the GiPSC, NCRM-5, and WTC-11 human induced pluripotent stem cell lines by altering seeding density and Chiron concentration. It is shown that high seeding density (137,000 cells per well) and low Chiron (3 µM) concentration produce the highest purity cardiomyocytes regardless of lineage, but that the level of purity is dictated by the genetic background of the cell type. As tissue engineering and regenerative medicine move closer to personalized medicine approaches, it becomes increasingly important to understand the implications of genetics in determining the differentiation potential of a patient’s own induced pluripotent stem cells for therapy and treatment purposes.
Notes:
Thesis (Sc. M.)--Brown University, 2018

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Citation

Irofuala, Chinedu, "Cardiac Differentiation Potential is Modulated by Genetic Background: Implications for Personalized Medicine" (2018). Biomedical Engineering Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/epz1-5d03

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