Stem Cell Factor or SCF is a small peptide that circulates throughout the bloodstream and eventually finds its way to the bone marrow where it summons bone marrow-based stem cells to the sight of injury for tissue repair purposes. Unfortunately, it takes injured tissues time to express SCF at high enough levels to recruit bone marrow stem cells to come and accelerate tissue healing. This is particularly the case in the heart after a heart attack. For this reason, scientists are trying to find new and better ways to increase SCF production in the damaged heart.
To that end, cardiologists at the Icahn School of Medicine at Mount Sinai have discovered that delivering SCF directly to damaged heart muscle after a heart attack seems to augment heart muscle repair and regenerate injured tissue.
“Our discoveries offer insight into the power of stem cells to regenerate damaged muscle after a heart attack,” said lead study author Kenneth Fish, Director of the Cardiology Laboratory for Translational Research, Cardiovascular Research Center, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai.
In this study, Fish and his colleagues used gene transfer to administer SCF to the heart shortly after inducing heart attacks in a pig model system in order to test its regenerative repair response. Fish and his coworkers developed a novel SCF gene transfer delivery system that stimulated the recruitment and expansion of adult cardiac stem cells directly to injury sites that reversed heart attack damage. In addition, the gene therapy improved cardiac function, decreased the death of heart muscle cells, increased regeneration of heart tissue blood vessels, and reduced the formation of heart tissue scarring.
“It is clear that the expression of the stem cell factor gene results in the generation of specific signals to neighboring cells in the damaged heart resulting in improved outcomes at the molecular, cellular, and organ level,” says Roger J. Haijar, senior study author and Director of the Cardiovascular Research Center at Mount Sinai. “Thus, while still in the early stages of investigation, there is evidence that recruiting this small group of stem cells to the heart could be the basis of novel therapies for halting the clinical deterioration in patients with advanced heart failure.”
The cell surface receptor for SCF is the c-Kit protein, and cells that possess the c-Kit protein are called c-Kit+ cells. c-Kit+ cells not only respond to SCF, but serve as resident cardiac stem cells that naturally increase in numbers after a heart attack and through cell proliferation are directly involved in cardiac repair.
To date, there is a great need for new interventional strategies for cardiomyopathy to prevent the progression of this disease to heart failure. Heart disease is the number one cause of death in the United States, with cardiomyopathy or an enlarged heart from heart attack or poor blood supply due to clogged arteries being the most common cause of the condition. Cardiomyopathy also causes a loss of heart muscle cells and changes in heart shape, which lead to the heart’s decreased pumping efficiency.
“Our study shows our SCF gene transfer strategy can mobilize a promising adult stem cell type to the damaged region of the heart to improve cardiac pumping function and reduce myocardial infarction sizes resulting in improved cardiac performance and potentially increase long-term survival and improve quality of life in patients at risk of progressing to heart failure,” says Dr. Fish.
“This study adds to the emerging evidence that a small population of adult stem cells can be recruited to the damaged areas of the heart and improve clinical outcomes,” says Dr. Hajjar.