The potential for ES cells to replace damaged or diseased cells in adult tissues has caused extraordinary interest in their therapeutic application. Dr. Lough’s research focuses on cardiac myocytes, which are found in the myocardium tissue, or heat muscles, that helps pump the chambers of the heart.
“After a patient has a heart attack, significant numbers of these cardiac myocytes die, and the damaged heart muscle is replaced by scar tissue that isn’t able to contract and help the heart beat. This problem is one of the biggest clinical issues faced by heart patients in the United States today,?says Dr. Lough.
In looking at ways to use ES cells, the research team had to consider the fact that the cells are “pluripotent,?meaning that they can develop into any of the 210 different cell types in the human body ?including tumors. That meant they had to determine how ES cells could be forced to become one single homogenous group of healthy cardiac myocytes to replace the damaged cells.
To address this problem, Dr. Lough looked at the way cardiac myocytes develop in the embryo itself. In research conducted on chick embryos since 1992, his team discovered that a group of very young embryonic cells called “precardiac endoderm?sends strong signals that cause adjacent cells in the embryo to become cardiac myocytes. Based on this finding, Dr. Lough reasoned that precardiac endoderm might similarly induce ES cells to become a homogeneous population of cardiac myocytes.
Working with Diane Rudy-Reil, Ph.D., a Medical College postdoctoral fellow, the investigative team recently discovered that chicken precardiac endode rm, when cultivated with mouse ES cells, makes them form rhythmically beating embryonic structures termed “cardiac embryoids.?Each cardiac embryoid contains a population of beating cardiac myocytes that is nearly homogeneous.
“The results are significant because we were able to induce the cells to transform the way we wanted them to. It’s a major step in ES cell research, but there’s still a long way to go. For example, we still don’t know if human cells will react in the same way,?Dr. Lough says. He notes, however, that the research has achieved unprecedented levels of success in this area.
Dr. Lough’s laboratory currently is developing support to expand these findings in several areas that will provide additional information. First, they want to identify the factors from precardiac endoderm that induce cardiac myocytes from ES cells. Then they want to determine if these findings are applicable to human ES cells. The ultimate goal is to find out whether cardiac myocytes from ES cells can repair diseased or damaged adult myocardium in non-human models. This last question is being answered in collaboration with John Auchampach, Ph.D., associate professor of pharmacology & toxicology, and Tim Nelson, Ph.D., a senior medical student.
Their findings were reported in the June 2004 edition of Circulation Research, a journal of the American Heart Association.
The study was funded by the National Institutes of Health.