A Change of Heart

BY RUTH SCHECHTER

WINTER 2007 -- Three-year-old Noelle Takagi goes to summer camp, loves to play in the water, shows a knack for drawing, and sings a mean karaoke. To her parents, these activities are genuine miracles. 

Noelle was born with a defective aortic valve that required open-heart surgery when she was 10 days old. At nine months, her replacement valve started leaking, and she faced the prospect of another difficult surgery or a transplant that had a 50 percent survival rate after five years.

Luckily, Noelle had a third option, and she became the youngest person to undergo a unique procedure that used a catheter to replace the valve without opening her chest. While the results have been positive, she still will require additional treatment as she grows older to replace the outgrown valve. ''I believe we made the right choice, but we appreciate that the doctors gave us options,'' says her father, Naoyuki Takagi. 

Each year about 40,000 infants are born with a heart defect in the United States. While new technology and surgical innovations have made a tremendous difference in the outcome and quality of life of these young patients, the harsh reality remains that an infant born with congenital heart disease often faces a future of repeated surgeries to replace an outgrown valve or one that has deteriorated from use. 

But breakthrough insights in stem cell biology and tissue engineering are pointing to a day when that situation finally may change. Research indicates that stem cells could play an important role in repairing damaged hearts, and that tissue engineering someday could be used to regenerate malformed or missing heart tissue. 

Packard physicians and Stanford scientists are developing a new Program in Cardiovascular Regenerative Medicine to apply the great potential of tissue engineering toward the creation of new ways to treat congenital heart defects and other cardiovascular diseases. 

Frank Hanley, MD (right)

''Regenerative medicine is a relatively new field, and we are still defining the niche areas that may have the highest impact,'' says Frank Hanley, MD, director of the Children’s Heart Center at Packard and the Lawrence Crowley, MD, Endowed Professor in Child Health. ''But the promise is immense, and so many lives could be dramatically improved by being treated with living, growing tissue rather than through surgery.'' 

Hanley and program co-director Michael Longaker, MD, director of the Children’s Surgical Research Program and the Deane P. and Louise Mitchell Professor in the School of Medicine, are helping to coordinate the work of Packard’s heart specialists with Stanford’s basic and clinical science investigators. While researchers continue to make great headway into the basic biology of stem cells and the process by which they differentiate and specialize, Packard physicians are identifying the most pressing needs and potential strategies to improve care for children with heart conditions. 

''At this point there is almost no heart defect we can’t repair with surgery. But there are limitations: prosthetic valves must be replaced as the child grows older, and transplanted tissue tends to deteriorate over time,'' says Hanley. ''But that’s what we have to work with in terms of reconstruction--we can’t make something out of nothing.'' 

An additional problem is that heart tissue is subjected to ongoing stress and strain: a valve, for example, moves 60 to 80 times each minute. 

These challenges make a coordinated, collaborative effort all that more important, says Longaker. ''While growing a replacement organ is still at least a decade away, the program may help get us to that point. It is designed to incorporate some of the most promising biomedical research under way into a comprehensive program that will accelerate the process of designing--and applying--new therapies.''

Noelle Takagi with her parents, Naoyuki (left) and Matsumi.

What makes the program unique and particularly promising, he adds, is its breadth of expertise. As part of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, the program integrates specialists from throughout the university, from chemists and biologists in the School of Humanities and Sciences to experts in business, law, engineering, physics, and biomechanics. 

''The program extends far beyond the boundaries of the medical center,'' says Longaker. ''The problems we need to solve come from the clinic, but the answers may come from some unexpected source. That’s why it’s so important we involve the entire university and organize teams: the answer is far beyond the scope of just one person.''

This new endeavor is very appealing to Naoyuki Takagi. ''When your child has a disease, one of the parents’ responsibilities is to provide the best health care available. For me, as a person from a different country, the care at Packard is something to be proud of. I thought that a miracle really happened to Noelle, and I’m happy that more improvements may happen.''

	Building a Better Valve Approximately eight out of every 1,000 children are born with a congenital heart condition. While these problems still can’t be prevented, great strides have been made in diagnosing and treating heart defects.  Noelle Takagi Defective heart valves usually are replaced with a mechanical heart valve made of plastic or Dacron, or of biologic material taken from a pig, cow, or deceased human donor. Like a normal valve, the replacement valve opens and closes with each heartbeat, permitting proper blood flow through the heart. After surgery, patients must take anticoagulant medications to prevent blood clots, and a child may face a half dozen or more operations over his or her lifetime.  An alternative involving tissue engineering would allow doctors to use a simple procedure to induce stem cells to specialize into a new heart valve, ready to place in the infant at birth. Because the valve would be living tissue derived from the baby’s own cells, it would grow and repair itself, and the child’s immune system would accept the material as its own.  Both Hanley and Longaker emphasize that there are many questions to answer before it will be possible to construct and introduce a replacement organ like a heart valve. Laboratory conditions cannot duplicate the complexity of a human being, and many factors involved in how cells differentiate and specialize still need to be clarified.