Dissertation Introduction

If I am doing this right, I just passed a major milestone in the composition of my doctoral dissertation: I wrote the first paragraph. Saving it for the end - the academic cherry on top of the ice cream called a PhD - helped me keep focused on the prize. I haven't been able to 'blog my thesis' like another stem cell researcher and blogger, so this is all you're going to get, or all you have to put up with.

In the United States, cardiovascular disease accounts for nearly 2 of 5 deaths, and each year, one million people experience a heart attack [1]. If a patient survives a heart attack, the heart recovers by replacing dead cardiac cells with a non-contractile scar. No innate regenerative capacity been identified for mammalian hearts [2-4], and no intervention to reconstitute myocardial function by muscle cell repopulation after injury has been approved for clinical use. Cell grafting is an attractive approach to restore cardiac function in the infarcted heart. Recent studies have identified several cell types that form living grafts in the heart, many of which have been shown to improve cardiac function [5-10]. Clinical trials with cells implanted from skeletal muscle or bone marrow are currently underway [11,12] even though major barriers for successful clinical success – graft integration and cell survival – still exist. The fibrosis that rapidly isolates the grafted cells from the host myocardium [13] is a prominent physical obstruction that can interfere with graft distribution and survival as well as electromechanical coupling. We have identified that genetic knockout of the matricellular protein, thrombospondin-2 reduces graft-related scarring. Apart from fibrosis, cell grafts face a basic challenge of survival [14]. If cells successfully engraft into the injured heart, about 90% of them do not persist three days after injection [15]. Immense increases in graft cell survival are needed if cell-based cardiac repair is to become a reality. In order to investigate potential treatments for myocardial infarction, we evaluated the regenerative capacity of mammalian cardiac tissue, identified an intervention to improve engraftment of cardiac cells and developed tools to improve the survival of embryonic stem cell derived cardiomyocytes injected into the heart.

Hopefully that is intelligible. It was written shortly before the timestamp on this entry...