Babies For Life Foundation

By Francis C. Assisi

27 September 2005 -- For the first time, scientists have discovered that injections of bone marrow stem cells can help rebuild weakened heart muscle, thanks to a technique pioneered by Dr. Amit Patel, one of the leaders in stem cell therapy for heart disease, at the University of Pittsburgh Medical Center.

Stem cells are primal undifferentiated cells which retain the ability to differentiate into other cell types. This ability allows them to act as a repair system for the body, replenishing other cells as long as the organism is alive. Medical researchers believe stem cell research, also called regenerative medicine, has the potential to change the face of human disease by being used to repair specific tissues or to grow organs. Still, as government reports point out, "significant technical hurdles remain that will only be overcome through years of intensive research."

Patel is director of the Center for Cardiac Cell Therapy at UPMC and the University of Pittsburgh McGowan Institute for Regenerative Medicine and is making the news these days with his pioneering work. .

For example, recently, it was discovered that a Pennsylvania woman with heart failure has significantly improved after undergoing a stem cell treatment in Thailand via the direct injection technique pioneered by Dr. Patel.

Jeannine Lewis suffered from non-ischemic cardiomyopathy. She was in Class III-IV heart failure (the borderline of needing a heart transplant) and on maximal oral medical therapy. After three months, MRI and echocardiogram results showed improvement and doctors have reclassified her to Class I heart failure – a significant improvement. Her shortening fraction and stroke volume have also increased.

In May Lewis became the first patient in the world to receive therapy using minimally invasive, direct cell injections to the heart. Dr. Patel accompanied Lewis to Bangkok in order to oversee her procedure.

Post-treatment, Lewis was in less pain and her exercise tolerance had increased greatly, “within weeks, my symptoms had greatly decreased while my energy level simultaneously increased. I am now able to clean my house, do my shopping and actively care for and play with my young child.” Lewis said. The recent quantitative test results now confirm what Lewis seems to have known from the beginning.

It's unclear if the stems cells used in the UPMC trials might become transformed into new heart muscle tissue or instead fuse with the patients' own damaged cells to help them work better. Alternatively, the stem cells could act like homing signals to attract other repair substances to the heart.

Last month, Dr Patel launched a second clinical trial to see if injections of bone marrow stem cells can improve the function of a weakened heart.

The trial will involve patients with ischemic heart disease who are scheduled for off-pump (beating heart) coronary artery bypass grafting surgery. In addition to assessing the safety and feasibility of using a patient's own stem cells as a potential therapy for heart disease, researchers also will be trying to determine just how many stem cells are needed to produce the best results.

Patients who give their consent to participate will be randomized to one of four treatment groups and neither they nor the researchers will know into which group they are assigned until the conclusion of the study. Researchers hope to enroll a total of 24 patients – six in each group – who they will follow over the course of one year.

"Stem cell therapy as an adjuvant to traditional bypass surgery is the next step to help determine the best way to help very sick heart failure patients. This is the first randomized study in the U.S. to evaluate the combination of cell therapy with traditional surgical revascularization and may help answer a number of key questions," explained Dr. Patel.

''When you inject these cells in, they act like a homing beacon to the heart," said Dr. Patel. ''The heart's just sending out an SOS signal saying 'Here! Come help me,' " he said. The adult stem cells then enlist other cells that deliver building blocks needed to partially restore heart function.

"Standard surgical and catheter-based treatments are reasonably effective for treating chest pain, reducing the risk of heart attack and improving heart function. But none has the ability to actually restore or repair damaged heart tissue. The aim of stem cell therapy is to repopulate the ailing heart muscle with cells that may help restore blood supply and help the heart regain its ability to contract more effectively and efficiently," added Joon S. Lee, M.D., clinical director of UPMC's Cardiovascular Institute and assistant professor of medicine and associate chief, division of cardiology, University of Pittsburgh School of Medicine.

Various studies that have been conducted around the world, including a limited number performed in the United States, have suggested that when patients with heart failure receive stem cells taken from their bone marrow, their hearts show signs of improved function and recovery. However, most of these clinical studies did not control for variables that may have influenced patients' clinical improvements, and all but a very few were designed as a randomized and double-blinded trial, the most rigorous method for evaluating clinical interventions.

UPMC researchers expect to ask about 75 patients to participate in the new trial in order to enroll and randomize six patients into each of the four study groups. A person not involved in the study will select a card from 24 numbered one through four to determine which group a patient is to be assigned. Then, with the patient under anesthesia, Dr. Patel's team will harvest bone marrow from the patient's hipbone. While the bypass operation is taking place, the patient's stem cells will be isolated from the bone marrow and prepared accordingly, depending on the patient's random assignment. Patients may be randomly selected to one of three groups that will receive varying concentrations of stem cells or to a fourth group receiving their own blood serum void of stem cells.

Though researchers have speculated that human embryonic stem cells might someday be used to regenerate either the heart muscle or the arteries feeding the heart muscle, the bone marrow stem cells being used in the UPMC studies likely would not work that way, Patel said. Rather, the stem cells may help the heart by fusing with injured cells and helping them function better. Another, even more likely mechanism -- but harder to prove -- is that the injected stem cells secrete growth factors or other substances that harness and redirect the body's healing powers.

Dallas-born Patel's interest in Stem Cell research stems from having seen "so many cardiac patients that we couldn't help with surgery or with traditional medications." Patel, 33, earned his undergraduate degree (B.S. 1993) and graduate (M.S. 1994) from Youngstown State University and then went on to earn his M.D. (1998) with distinction from Case Western Reserve University. He received additional training at Baylor University Medical Center and University of Pittsburgh Medical Center. Among the many awards Patel has received, is the Most Distinguished Resident Award from the American Association of Physicians of Indian Origin (AAPI) at the 21st Annual Convention, Orlando, FL.

francisassisi@hotmail.com