Press Release

Human Myoblast Injection into Porcine Heart

P. Law, J. Weinstein, H. Leonhardt, S. Ben-Haim, S. Williams, Q. Fang, T. Hall, T. Goodwin

Heart muscle degeneration is the leading cause of debilitation and death in humans. Heart Cell Therapy aims to repopulate the dying heart with living muscle cells, increasing heart contractility, thus improving the quality of life and lengthening the lifespan of heart patients. We report here the first direct evidence demonstrating the feasibility and safety of delivering human embryonic skeletal muscle cells called myoblasts into the pig heart using an injection catheter. Cells were injected through a catheter (Myostar, Biosense Webster, Johnson & Johnson) threaded through a thigh artery into the left chamber of the heart. Approximately one billion human myoblasts were injected through a needle timed to protrude 6mm from the tip of the catheter into the heart muscle. Twenty injections were made having volumes of 0.1, 0.2, 0.3, 0.5, 1.0 ml, and cell concentration of 100 million per ml. There were no significant changes in heart rate, electrocardiogram and temperature throughout the experiment. Passage through the injection catheter caused less than 5% cell death.

At the completion of the procedure, the heart was processed for examination. There was no perforation of the injected heart. Human myoblasts were found widely and evenly distributed throughout the muscle wall where the cells were injected. A similar study using the Bioheart catheter yielded comparable results.

In Arizona Heart Institute, Heart Cell Therapy involves taking about 5 grams of thigh muscle under local anesthesia from the heart patients. From this biopsy, about one billion purified myoblasts are grown in a sterile laboratory in about 30 days. These cells will then be delivered with 20 injections placed 1 cm apart between the viable (healthy) and infarcted (damaged) areas. Injections can be made through catheters or under direct visualization in an open-heart bypass surgery.

Heart Cell Therapy makes available the patient's own muscle cells to repopulate the infarct, secreting the various regenerative factors and depositing contractile proteins to regain heart function.

Heart Cell Therapy is a new frontier of Myoblast Transfer Therapy, a platform technology of cell therapy, gene transfer and tissue engineering. Cultured normal myoblasts, when injected into degenerative muscles, fused among themselves, forming normal muscle cells to replenish degenerated ones. They also fused with the host muscle cells, inserting their nuclei and thus the human genome, to effect genetic repair.

Over 230 myoblast transfer procedures in the last 10 years demonstrated no severe adverse event in treating neuromuscular diseases, culminating in a 19% increase in breathing capacity and a 123% increase in strength when 50 billion myoblasts were injected into 80 muscles of Duchenne Muscular Dystrophy patients. Two months of immunosuppression was sufficient to prevent rejection of foreign donor cells called an allograft. Upon review of the study, the FDA encouraged Phase III multicenter clinical trial of myoblast transfer on muscular dystrophy.

Since our initial human myoblast transfer into the porcine heart, deliniating study parameters such as cell number, cell concentration, injection volume, and delivery method, human Heart Cell Therapy has begun. By now more than 10 patients suffering from congestive heart failure have received myoblast injections in conjunction with open-heart bypass surgery in France and the USA. Reportedly two died unrelated to the myoblast administration, and the rest are in stable condition. Some have demonstrated improved heart function since myoblast transfer. One patient received myoblasts through a catheter. All patients used their own myoblasts as autografts.

Like muscular dystrophy, genetically defective hearts will need myoblasts from foreign normal donors. Such allografts will be necessary for treating heart patients with infectious diseases to avoid contamination of the sterile culture laboratories. Allografts utilize well-characterized myoblasts that are available, allowing Heart Cell Therapy to occur within 12 hours of myocardial infarction and potentially eliminating scarring upon regeneration. Scarring is unavoidable in an autograft in which the patient's own myoblasts take 3 to 4 weeks to grow.

Whether autografts or allografts, Heart Cell Therapy is the most logical alternative in prevention and in treatment of heart conditions due to congestion, aging, heredity or trauma. It may be used to enhance heart contractility in anti-aging.

Today, the field of Cell Therapy is perplexed at the controversial stem cell research, whereas Gene Therapy research is tainted by the mishaps of "viral vector" technology. Myoblast Transfer Therapy does not involve the use of controversial stem cells or the use of dangerous viral agents that have been the cause of death in recent trials. It has been proven safe on over 230 human procedures in the past ten years.

Stem cell technology has gained much attention due to the controversy of utilizing cells from human embryos. More critically, scientists do not know the specific factor(s) that trigger stem cells to differentiate only into heart muscle cells, and not into other cell types. Such knowledge is not likely to be available within ten years. Until then, stem cell transplant into the heart may result in bony, cartilageous, fatty and fibrotic elements that are detrimental to heart function. Unlike the pluripotent stem cells, myoblasts are differentiated cells destined to become muscle. Cardiovascular disease is the number one cause of death, and more than $280 billion is spent each year globally in its combat. Heart muscle cells are terminally differentiated and do not divide significantly to regenerate the damaged heart muscle. When compared to a heart transplant, Heart Cell Therapy eliminates the use of lifelong immunosuppressant, which is a major cause of infection and death of heart transplant patients. Heart Cell Therapy is much less invasive, and tissue availability is not an issue. At a fraction of the cost of a heart transplant, it promises health cost reduction.