Ten people in Europe are making medical history. Their damaged hearts have all been rejuvenated with the help of implanted cells taken from their thighs. The technique was pioneered by a tiny Fort Lauderdale startup called Bioheart Inc., and it is groundbreaking for a number of reasons--not least because it offers hope to millions of heart attack victims. But the technique also marks an important step forward in the nascent field of medicine known as tissue engineering. Scientists have successfully prodded the human body into regrowing skin, cartilage, bone, and even corneas by manipulating cells. The Bioheart patients, however, represent one of the first successes in regenerating portions of a far more complex organ.
It is still very early days for this technique, known as myogenesis, but it is already generating considerable buzz among heart disease specialists. Status reports on the 10 patients will be given at a special session during the American Heart Assn. annual meeting in mid-November. Guidant Corp. (GDT
), a maker of medical devices, was intrigued enough to invest $1.5 million in two-year-old Bioheart in June. And another tissue engineering company, Osiris Therapeutics Inc., is developing a similar technique, which has yet to be tested in humans. "We don't have many good options" for treating heart attacks, says Dr. Donald D. Glower, professor of surgery at Duke University Medical Center. "This is one of the more promising avenues. It could eventually become a very, very powerful tool."
In fact, tissue regeneration may be the most promising development in the treatment of heart disease since the advent of transplants. The need is certainly desperate. Heart disease is the biggest killer in the industrialized world, responsible for one out of every 2.5 deaths. Over 17 million people in the U.S. have coronary disease, and 7 million suffer heart attacks each year.
Heart disease is so deadly because, unlike most organs in the body, the heart does not grow new cells to replace worn ones. When heart cells die during an attack, usually because they are deprived of oxygen, that portion of the heart becomes dead tissue. The rest of the organ must work that much harder to compensate, until it fails as well.
The best cure is a heart transplant. But the shortage of available organs, not to mention the dangers inherent in the process, makes this an impossible solution for most patients. So for the past 30 years scientists have been searching for a way to regenerate heart tissue.
Enter Howard J. Leonhardt, founder and CEO of Bioheart. Leonhardt sold off the first company he started, a maker of cardiac stents, in 1998. That summer he was watching TV and happened to catch the movie Superman, in which Clark Kent's father dies of a heart attack. He was inspired to come up with a solution to this disease and started Bioheart that August. Leonhardt soon assembled a team of scientists to study cell types that might be used to regenerate heart tissue.
VITAL CHOICE. Most of the research into myogenesis, done in academic labs, has focused on embryonic or adult stem cells, the precursors to all the body's tissues. But the Bioheart team found no way of ensuring that the stem cells turned into heart, as opposed to bone or cartilage. Heart muscle cells were also considered, but these could fall victim to the same lack of oxygen that killed the original cells.
Muscle cells such as those in the thigh, in contrast, are far more robust and able to repair themselves. Since the heart is also a muscle, it did not seem that much of a leap to combine the two. "It made sense to me as a muscle molecular biologist," says Doris A. Taylor, an associate professor at Duke University Medical Center and chairman of Bioheart's scientific advisory board. "One of the really nice things about this technique is that it is very straightforward."
Straightforward, but not simple. The patient first has a silver-dollar size portion of thigh muscle removed. The tissue is sent to a Bioheart lab, where it is put through an 18-step process to select out and multiply immature muscle cells, called myoblasts. The process takes 21 days, and every step must be strictly controlled, says Leonhardt: "Even one minute off can ruin the cells."
Once the myoblasts are ready, they are shipped back to the hospital. Using a specialized catheter, 10 to 30 pellets, each consisting of some 50 million cells, are injected in and around the damaged area of the heart. New cells integrate into the area within three weeks, with about eight weeks needed for functional improvement, says Leonhardt. Because the original cells are taken from the patient, there is no danger of rejection.
POSITIVE SIGNS. So far, the catheter procedure has been tried on a 78-year-old woman in Rotterdam, in June. Two other patients in Europe are waiting for their myoblasts to be processed and will likely be operated on in December. However, Dr. Phillippe Menasche of Hospital Bichat in Paris has implanted Bioheart-cultured cells in nine patients since June, 2000, during open-heart surgery.
One of Menasche's patients died after the operation, but the other eight, as well as the woman who received her cells via catheter, have all shown measurable improvement. Intriguingly, the new cells didn't turn into heart tissue, which would leave them vulnerable to the same disease that destroyed the initial cells. Instead, they retain most of the characteristics of hardy myoblasts.
There are still many questions, however. Menasche notes that with his patients, it could be the bypass surgery that produces the improvement. Controlled clinical trials must be conducted to determine the therapeutic benefit of the myoblasts. Bioheart plans to file an application with the Food & Drug Administration this month for permission to start clinical trials in the U.S.
There are also concerns about whether the implanted cells will remain stable over time. "We really don't know, and have no good way of knowing, what the cells are doing in vivo," says Taylor. Still, she says, "we don't necessarily have to know, as long as it works." Heart disease patients would surely agree.
By Catherine Arnst in New York
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