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Timely intervention

Clinical trial participant Patty Bilkey says she feels great — and ready to chase after grandson Harvey Perkins. (Photo: Scott Streble)

Can a patient’s own stem cells repair a damaged heart? Clinical research holds the answer.

By Jeanne Mettner

When 66-year-old Patty Bilkey experienced sudden fatigue on a Monday in late June last year, she attributed it to the only reasonable explanation she could think of — overdoing herself during a “girls’ weekend” away.

But when her skin became clammy and she began experiencing flu-like symptoms with a slight pain in her left arm, she became more concerned.

“I remember I was sitting at the computer that morning, looking up ‘how to get more energy’ when it dawned on me that I should instead be doing a search on signs of a heart attack,” Bilkey says.

Bilkey’s husband rushed her to Fairview Southdale Hospital, where she learned that she had had a massive heart attack. There she received an angioplasty and two stents to open her blocked heart vessels — and an invitation to participate in leading-edge research offered through the hospital’s partnership with University of Minnesota Medical Center, Fairview.

For decades, the University of Minnesota has been pioneering ways to improve the lives of people who have heart disease — from early diagnosis to heart transplants and ventricular assist devices. Today it is a leader in an emerging area of study: stem cell treatments to repair damaged hearts.

A chance to help the heart recover

That expertise would prove beneficial to Bilkey. Two days after her heart attack, she was invited to participate in a groundbreaking multicenter study funded by the National Institutes of Health known as Late TIME (Transplantation in Myocardial Infarction Evaluation), which is designed to evaluate whether implanting a patient’s own stem cells into the heart two to three weeks following a heart attack could help to safely and effectively improve cardiac function. If she agreed to enroll, Bilkey would be assigned either to a “treatment” group that receives an injection of millions of stem cells from their own bone marrow or to a “standard care” group that receives a placebo injection.

“My immediate response was, ‘Where do I sign?’” recalls Bilkey. “I felt like I had nothing to lose.”

Three weeks later, she received her injection. Because it’s a double-blind study (see sidebar), neither she nor her doctors will know whether she received stem cells or a placebo until later this fall. At that time, the data will be “unblinded” and analyzed, and some of the study results will be released.

In addition to Late TIME, University researchers are participating in a similar national, multicenter trial known simply as TIME, which is evaluating the success of the same stem cell therapy given just three to seven days after the patient’s heart attack.

Since the two studies began in 2010, more than 200 people have enrolled nationwide. Ten of them are at the University.

“The University of Minnesota has a long-standing tradition in both transplantation and cell therapy initiatives,” explains Daniel Garry, M.D., Ph.D., chief of the Medical School’s Division of Cardiology and executive director of the Lillehei Heart Institute. “Our goal with these studies is to look critically at the benefits of using a patient’s own cell therapy following a heart attack.”

Led by interventional cardiologist Ganesh Raveendran, M.D., the cardiac cell therapy research team includes Garry, cardiologist Cindy Martin, M.D., cardiothoracic surgeon Ranjit John, M.D., and research nurses Emily Caldwell, B.S.N., R.N., and Barbara Bruhn-Ding, B.S.N., R.N.

“There is no doubt that in recent decades, we have continued to significantly improve treatments for patients who have had heart attacks. Despite this, their heart function doesn’t recover as well as it should,” says Raveendran. “Ultimately, we hope that cell therapy will improve cardiac outcomes and quality of life for these patients.”

Ranjit John, M.D., directs the University's Ventricular Assist Device Program. (Photo: Scott Streble)

Stem cells and devices

In addition to helping to boost heart function after heart attacks, stem cell therapy may also be boosting the effectiveness of mechanical treatments for heart failure.

The U.S. Food and Drug Administration has recently authorized the team to conduct another study. Starting this fall and exclusively at the University, 24 patients with severe heart failure will receive either injections of their own stem cells or a placebo injection during the implantation of a left ventricular assist device (LVAD).

LVADs are implanted pumps that help maintain adequate circulation in patients with severe heart failure. In some cases, LVADs allow hearts to rest and recover. In other cases, they can be used as a “bridge” therapy until the patient can get a heart transplant, or when transplantation is not an option, LVADs can provide permanent circulatory support.

The University’s study will be one of the first in the nation to examine the effects of stem cell therapy during LVAD placement. It’s a natural extension of the successes the University has had since its physicians began using LVADs in 1995. Still national leaders in this field, University doctors implant nearly 80 LVADs each year.

One-third of the patients in this LVAD cell therapy study will receive a placebo injection during the pump implantation surgery, while the other two-thirds will receive millions of their own stem cells. If patients in the study eventually get heart transplants, researchers will examine their native hearts to determine whether bone marrow stem cells have grown into cardiac cells.

“The holy grail of end-stage heart failure remains myocardial recovery, so our hope is that this therapy will help the heart recover better,” says John, who directs the University’s Ventricular Assist Device Program. “After a period of three to six months, we will gradually wean down the support given by the LVAD — then determine whether the function of the native heart is improving.”

A prelude to new achievements

Throughout the past several years, investigators from seven of the University’s basic science laboratories have been focusing on human stem cells and their ability to give rise to heart cells — the results of which have helped clinical researchers fine-tune their work in preparation for these studies.

Preclinical animal studies conducted here have also contributed to this research, as has the Minnesota Molecular and Cellular Therapeutics facility on the St. Paul campus, one of only three centers in the world that processes cells for cell-therapy research and treatment.

“All of the basic science work, coupled with our experience in implanting LVADs and in processing stem cells, has served as a prelude to the innovative clinical investigations we are doing now,” Garry says.

Ganesh Raveendran, M.D., who leads the TIME trials for the University, finds clinical research participants' optimism rewarding. (Photo: Scott Streble)

A positive effect

Raveendran finds it rewarding to see patients become more optimistic about their prognoses — even if they don’t know whether they’ve received the stem cell therapy or a placebo.

“In this study, patients are eager and enthused,” he says. “They know that there is a two-in-three chance that they will receive stem cells, and this brings a tremendous amount of hope to them.”

For Bilkey, participating in the study has come with no regrets. After her heart attack, her heart’s ability to pump blood was reduced by half. Today tests show that her heart’s pumping function is nearly normal.

Bilkey looks forward to her main sources of daily physical activity — walking, riding her stationary bike, and keeping up with her 6-year-old and 1-year-old grandkids.

“I definitely feel better than before I had the heart attack,” says Bilkey. “I really see no negatives through my participation in this study at all. If I had to do it all over again, I certainly would.”

In a heartbeat, perhaps.

Jeanne Mettner is a Minneapolis-based writer who specializes in medicine and health.

To make a gift to support heart cell therapy research at the University of Minnesota, contact Amanda Storm Schuster at 612-626-2475 or a.schuster@mmf.umn.edu.

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