UF to research stem cell treatments for heart disease

University of Florida researchers will play a key role in a new national network designed to study stem cell treatments in patients with cardiovascular disease.

As part of a five-member consortium known as the Cardiovascular Cell Therapy Research Network, UF scientists will seek to identify and test new cell therapies to improve the structure and function of the heart and its blood vessels. The network and its projects will be supported by a grant from the National Heart, Lung and Blood Institute that is expected to total $33.7 million over the next five years. Approximately $5 million will be disbursed in 2007.

The centers will begin meeting immediately to select protocols and then screen patients for possible entry into multiple research trials in cardiovascular regenerative medicine set to launch early this year. The collaboration will enable study investigators to rapidly boost sample sizes and expedite studies that otherwise would likely take many years to complete. At least 10 studies are planned during the funding period.

The other centers are the Cleveland Clinic, the Texas Heart Institute, the University of Minnesota and Vanderbilt University. The network's data coordinating center will be based at the University of Texas Health Science Center in Houston; the NHLBI project office is in Bethesda, Md.

"Most of us believe that some form of regenerative medicine will be the future for treatment of cardiovascular disease, that it will be the next level of care," said Carl J. Pepine, M.D., a professor and chief of cardiovascular medicine at UF's College of Medicine and the principal investigator and center director for the UF site.

Researchers will focus on adults with coronary artery disease, congestive heart failure or other conditions, including diabetes, that reduce blood flow to the heart, damaging heart muscle and hampering its ability to function properly. As a result, the quality of life of many of these patients becomes very poor, as they are progressively unable to participate in their usual day-to-day activities.

"These will be patients who have already had medical therapy, bypass surgery, angioplasty, stents or other treatment options and have not responded to those treatments," Pepine said. "The current thinking is we have a limited capacity to repair our hearts and blood vessels but that is somehow defective in people who have end-stage disease. Our hope is that by providing new cells we may be able to restore the reparative process."

Network scientists met last week to discuss the initial study protocols they'll pursue from a pool of 10 submitted during the grant application process. Studies will test whether various cell therapies can improve the heart's plumbing by helping to repair blood vessels or form new ones and strengthen the heart muscle to improve its ability to pump efficiently.

"In the United States we have had difficulty amassing the numbers of patients and also bringing together the multiple disciplines required to perform stem cell therapy at one table to be able to have large enough trials to prove the worthiness of cell therapy in cardiovascular diseases," said Chris Cogle, M.D., an assistant professor of medicine at UF's College of Medicine who has expertise in stem cells and bone marrow transplantation. "This is the raison d'etre of the network, to amass the resources, bring the necessary people to the table and recruit patients who need this help to be able to complete these trials and answer whether or not cell therapy can help prevent heart disease or protect patients who have it.

"We may have new options for patients whose cardiologists might have told them there's nothing else they can do," he said.

Projects likely will involve the use of stem cells obtained from a patient's own bone marrow or peripheral veins'or even from the heart itself'and will incorporate new strategies for cell delivery to the heart and techniques for screening and localizing transplanted cells. In some studies the cells may be treated to enhance their function before they are returned to the body. For example, UF investigators have found that exposing these cells to nitric oxide, low oxygen levels, low temperatures or even gene therapy enhances their ability to restore function in animal models. Methods of delivering the cells to the blood vessels or directly into scarred heart muscle also will be tested.

UF scientists also have proposed one study that involves extracting skeletal muscle cells from the thigh in patients with severe heart failure who are awaiting heart transplantation. The cells would be multiplied in tissue culture and then implanted directly into the same patient's heart. The goal would be to determine whether the cells can strengthen a very weakened heart and determine how long the cells survive, said Daniel Pauly, M.D., Ph.D., an associate professor of medicine and director of the division of cardiovascular medicine's molecular cardiology and genetics section at UF's College of Medicine.

Researchers will include experts in various disciplines, such as hematology, nephrology, radiology, stem cell biology, cardiovascular medicine, pediatric cardiology and cardiothoracic surgery. In addition to Pepine, Cogle and Pauly, they include nephrologist Mark Segal, M.D., Ph.D.; pediatric cardiologist Barry Byrne, M.D., Ph.D.; endocrinologist Maria Grant, M.D.; cardiothoracic surgeon Thomas Beaver, M.D.; vascular surgeon C. Keith Ozaki, M.D.; John Wingard, M.D., director of UF's Blood and Bone Marrow Transplant Program; stem cell biologist Edward Scott, Ph.D.; and radiologist John Forder, M.D. Pulmonologist Veena Antony, M.D., will chair the Internal Advisory Committee.

They will work closely with various university facilities to obtain and process the cells used in the research, including the bone marrow transplant unit, and the Good Manufacturing Practices facility at the Center of Excellence for Regenerative Health Biotechnology, directed by Richard Snyder, Ph.D., who heads biotherapeutic programs in UF's Office of Research and Graduate Programs.