One of the research institutions that has been at the forefront of developing investigational stem cell treatments for heart attack patients is The Cedars-Sinai Heart Institute. Recently, a research team at Cedars-Sinai Heart Institute (CSHI) has injected cardiac stem cells into the hearts of laboratory mice afflicted with a rodent form of Duchenne muscular dystrophy. This disease can also adversely affect the heart, and these stem cell injections actually improved the heart function of these laboratory animals and resulted in greater survival rates for those mice. This work might provide the means to extend the lives and improve the quality of life of patients with this chronic muscle-wasting disease.
The CSHI team presented their results at the American Heart Association Scientific Sessions in Chicago. Their results clearly demonstrated that once laboratory mice with Duchenne muscular dystrophy were infused with cardiac stem cells, the animals showed progressive and significant improvements in heart function and increased exercise capacity.
Specifically, 78 lab mice that had been given laboratory-induced heart attacks were injected with their own cardiac stem cells, and over the next three months, these mice demonstrated improved pumping ability and exercise capacity in addition to a reduction in heart-specific inflammation. The CSHI team also discovered that the stem cells work indirectly, by secreting tiny vesicles called exosomes that are filled with molecules that induce tissue healing. When these exosomes were purified and administered alone, they reproduced the key benefits of the cardiac stem cells.
Apparently, this particular procedure could be ready for testing in human clinical studies as soon as next year.
Duchenne muscular dystrophy or DMD is a genetic disease that results from mutations in a gene found on the X chromosome in humans. DMD affects 1 in 3,600 boys and is a neuromuscular disease caused by abnormalities in a muscle protein called dystrophin. Because dystrophin is an important structural protein for muscle that anchors muscle to other muscles and to the substratum, deficiencies for functional copies of the dystrophin protein cause progressive muscle wasting, destruction, and muscle weakness.
The majority of DMD patients lose their ability to walk by twelve years of age, although the severity of the disease varies from patient to patient. The average life expectancy is about 25, and the cause of death is usually heart failure. Dystrophin deficiency causes heart muscle weakness, and, ultimately, heart insufficiency, since the chronic weakness of the heart muscle prevents the heart from pumping enough blood to maintain a regular heart rhythm and provide for the needs of the rest of the body. Such a heart condition is called “cardiomyopathy.”
“Most research into treatments for Duchenne muscular dystrophy patients has focused on the skeletal muscle aspects of the disease, but more often than not, the cause of death has been the heart failure that affects Duchenne patients,” said Eduardo Marbán, MD, PhD, who is the director of the CSHI and the principal investigator of this particular study. “Currently, there is no treatment to address the loss of functional heart muscle in these patients.”
In 2009, Marbán and his team completed the world’s first procedure in which a patient’s own heart tissue was used to grow specialized heart stem cells. Stem cells from the heart were isolated, cultured, and then injected back into the patient’s heart in order to repair and regrow healthy heart muscle that had been injured by a heart attack. Results, Marbán and his colleagues published these results in The Lancet in 2012, and also demonstrated that one year after their patients had received the experimental stem cell treatment, they showed significant reductions in the size of the heart scar that had been produced by their heart attacks.
Earlier this year, CSHI researchers commenced a new clinical trial entitled “ALLSTAR,” which stands for Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration (Clinical trial number NCT01458405). In this study, heart attack patients are given injections of stem cells from healthy donors, which should work better than the patient’s own stem cells, which were damaged by the heart attack.
CSHI has recently opened the nation’s first Regenerative Medicine Clinic, which is designed to match heart and vascular disease patients with the appropriate stem cell clinical trial being conducted at CSHI and other institutions.
“We are committed to thoroughly investigating whether stem cells could repair heart damage caused by Duchenne muscular dystrophy,” Marbán said.
The protocols for growing cardiac-derived stem cells were developed by Marbán when he was on the faculty of Johns Hopkins University. Johns Hopkins has filed for a patent on that intellectual property and has licensed it to Capricor, a company in which Cedars-Sinai and Marbán have a financial interest. Capricor is providing funds for the ALLSTAR clinical trial at Cedars-Sinai.