Basic Science Projects

The heart can repair itself. The question is how?

Photo courtesy of Cell

Photo courtesy of Cell

The heart has long been perceived as a terminally differentiated organ with no repair capacity. Our group is challenging this paradigm based on our recent work that demonstrates the heart’s ability to generate new heart muscle cells in adults. Our work leverages a novel application of carbon-14 (14C) dating that exploits changes in atmospheric 14C due to above surface nuclear bomb tests during the Cold War era. This variation in 14C due to nuclear testing allows us to date objects originating from the 1950s until today accurate to within one year as opposed to previous methods which could have a variance of  100 years. Using this technique, we dated the DNA—which is formed when a cell is generated—and estimated the age of heart muscle cells. This information allowed us to estimate the average age of these cells to be six years younger than the individual, providing strong evidence for generation of new cardiac muscle cells in the human heart after birth. We have also shown that this regenerative capacity is present throughout the heart. The question is, of course, which cell types have this capacity to generate new heart muscle cells and how do they do so? Our goal is to identify these cell types and their regulatory mechanisms to allow us to stimulate the heart to mend itself. These research questions span several of our team’s projects.

Can we generate multiple types of new heart muscle cells?

The heart comprises several different kinds of cells: connective tissue cells (fibroblasts), vascular cells (smooth muscle cells, endothelial cells) and heart muscle cells (cardiomyocytes). Within these main subtypes there exists further diversity. For example, heart muscle cells may be one of several subtypes— pacemaker cells, nodal cells, Purkinje fiber cells, atrial heart muscle cells or ventricular heart muscle cells. We have shown that peripheral blood cells can be reprogrammed into immature induced pluripotent stem cells (iPSCs), which are then used to generate different kinds of heart muscle cells. Projects included in this line of research involve single-cell technologies, genome editing tools, and gene expression analysis through molecular beacon technology. We are also developing technologies to generate 3-D structures to support these cells during transplantation.