Fourth Annual Public Interest Organization Meeting
Research Presentation: The Potential of Stem Cells for Treatment of Ischemic Heart Disease
February 5, 2003 - Bethesda, Maryland
Dr. Richard Cannon, Clinical Director, Division of Intramural Research, NHLBI, described research on the therapeutic
potential of stem cells for ischemic heart disease. This exciting area of research is based on the concept that
human cells have the potential to heal damaged tissues in the body, for at least some diseases and conditions. Stem
cells are primitive precursor cells that are found in most organ systems of the body, even in adults. They have the
ability to renew themselves and to become specialized cells in many organ systems.
Adult stem cells may have considerable potential for treating a variety of diseases. For example, stem cells from bone
marrow and muscle have recently been injected into heart muscle in an attempt to generate heart tissue in a few patients
who have severe atherosclerotic coronary heart disease (CHD) with extensive damage to heart muscle. Bone marrow cells
containing stem cells have been administered to hearts in small groups of patients with recent heart attacks, with reports
of improved heart function compared with untreated heart attack victims.
Researchers have focused on a newly described pathway of differentiation for stem cells derived from bone
marrow. The hematopoietic pathway, whereby precursor stem cells in the bone marrow form hematopoietic
(blood-forming) cells, has been known for several decades. The endothelial pathway, whereby precursor stem cells
in the bone marrow form endothelial progenitor cells (EPCs) that enter the circulation and differentiate into endothelial
cells, was recently discovered by researchers in Boston headed by the late Dr. Jeffrey Isner, a former NHLBI investigator.
Endothelial cells line the inner surfaces of blood vessels and the heart. The purpose of EPCs in the circulation may be to
attach to areas of injury and promote healing of damaged tissue. Unfortunately, an individual's ability to release EPCs
into the circulation diminishes in the presence of major risk factors for atherosclerosis (e.g., high blood pressure, high
cholesterol levels, smoking, diabetes, aging).
Building on experimental studies in mice, clinicians infused EPCs directly into the hearts of patients whose heart
muscle has been damaged by heart attacks. Within 3 months, these patients had improved heart function and
increased blood flow compared with untreated heart attack patients.
Dr. Cannon and his colleagues are currently exploring a complementary approach, using granulocyte
colony stimulating factor (G-CSF) to boost the number of stem cells within the bone marrow and release
them into the circulation. Once in the circulation in sufficient numbers, these cells may be attracted
to areas of heart injury or diminished blood flow due to coronary artery disease, and transform into new
blood vessels and heart muscle. Again based on the success of experiments in mice, the investigators are
pursuing this approach in a clinical trial with patients who have severe CHD and have failed all conventional
treatments. The hypothesis is that G-CSF mobilization of stem cells and EPCs from the bone marrow will
ultimately result in increased the blood flow in ischemic heart tissue and and improved contraction of heart
The investigators have already demonstrated the safety of this approach in a Phase I study and are currently
addressing the efficacy of the approach in a Phase II study. Medical students in Dr. Cannon's laboratory are
trying to determine whether any specific characteristics of EPCs predict the success of this approach and what
genes influence success. For future studies, they are considering different ways of labeling the EPCs to track
their movement and determine whether they "home" to heart muscle.
Dr. Cannon emphasized that these studies involve many researchers, with multiple talents and skills, from the
NHLBI and other ICs. In discussion, he commented that the response of patients (e.g., with neutropenia) to the
G-CSF approach varies and, at this early stage of the research, investigators do not yet understand how G-CSF
stimulates cell differentiation or the reasons for this variability. Researchers are continuing to search for
other stimulatory factors that might boost EPCs more potently than G-CSF.