National Center For Regenerative Medicine Researchers Find Innovative Methods For Treating Heart Attacks

Main Category: Cardiovascular / Cardiology
Article Date: 03 May 2007 - 14:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

Heart attacks are the leading cause of death in both men and women, with over 450,000 deaths in the United States each year. Improving the treatments available to patients who have survived a heart attack is therefore imperative. Researchers from the National Center for Regenerative Medicine (NCRM) have identified two innovative and distinctly different methods to help treat patients recovering from a heart attack.

The first study showed that cell-based gene therapy to regenerate damaged cardiac muscle tissue and improve mechanical cardiac function was feasible using skeletal muscle stem cells modified to express a stem cell honing signal. The second study showed that bone marrow stem cells could emerge as a valuable treatment for repairing damaged hearts by regenerating damaged heart muscle and maintaining the electrical conduction across the heart. The researchers believe that combining cell and gene therapy can enhance the effects of cell transplantation and optimize regeneration of tissue in the heart.

The team of NCRM investigators, including Assistant Professors of Medicine and Biomedical Engineering at Case Western Reserve University, Marc Penn, M.D., Ph.D., Director of the Earl and Doris Bakken Heart-Brain Institute at Cleveland Clinic, and Kenneth Laurita, Ph.D., MetroHealth Medical Center, recently published the results of two studies which suggest new, more effective ways of treating heart attacks. Heart attacks, also known as myocardial infarctions, occur when the blood supply to part of the heart is interrupted, resulting in damage or death of the tissue. Damaged cells in the heart then send out a "S.O.S" signal called stromal-cell derived factor-1 (SDF-1) to mobilize stem cells from the bone marrow to travel to the damaged tissue and begin repair. Even with some repair by these cells, scar tissue forms where the heart was damaged and leaves patients at risk for arrhythmias due to the scar tissue's slower electrical conduction as compared to healthy muscle tissue. The result of this change in electrical conduction across the heart muscle is called arrhythmia and is a condition in which the heart beats either faster or slower than normal. Although some arrhythmias are benign, many are fatal, particularly those that are caused by heart attacks.

In previous cardiac research, investigators at the NCRM used undifferentiated skeletal muscle stem cells to regenerate damaged heart tissue. The stem cells' purpose was to develop into new heart muscle and reduce the amount of scarring thereby improving heart function. In a recently published article in Human Gene Therapy, Drs. Penn and Laurita genetically modified skeletal muscle stem cells to express SDF-1 for up to 21 days after implantation. Echocardiography was used to quantify changes in cardiac function, and optical mapping was used to determine the arrhythmogenic risk. Eight weeks after cell therapy, the investigators observed a 70% increase in vascular density in the hearts of SDF-1-treated animals as compared to animals only receiving the skeletal muscle cells. Optical mapping revealed that all animals receiving these cells had increased arrhythmia whereas only 50% of control animals had this problem.

Since this therapy was effective but resulted in an increase in arrhythmia risks, the NCRM team investigated the use of bone marrow derived mesenchymal stem cells to enhance the electrical viability of heart muscle damaged by a heart attack. From their publication in the Journal of Molecular and Cellular Cardiology, this research team studied four groups of rats: normal, those with infarcted hearts but no treatment, those with infarctions and muscle stem cells implanted, and those with infarctions and bone marrow stem cells implanted. For the animals receiving bone marrow stem cells, it was observed that the electrical viability was preserved and there was no increase in arrhythmia risk. As in the first study, risk of arrhythmia was increased in animals receiving skeletal muscle cells.

The results in both studies are important and require attention because they hold the potential for more efficient and effective heart attack treatments. By combining the results of both studies, these investigators are unlocking new ways to naturally and safely heal a patient using the patient's own cells after a heart attack. "The goal of cell therapy to date has been to improve heart function, our studies demonstrate that the electrical and mechanical effects of cell therapy are independent, and need to be addressed in order to offer patients the greater improvement possible" says Dr. Penn. In ongoing studies, these researchers have combined the results of these two studies and are investigating the use of bone marrow stem cells genetically modified to express SDF-1. They believe this will address both mechanical and electrical consequences of cell-based gene therapy and become the future in treating patients who have suffered a heart attack.

A leader in basic and clinical research utilizing non-embryonic stem cells, the NCRM's central administration is located in the Iris S. & Bert L. Wolstein Research Building on the campus of Case Western Reserve University in Cleveland, Ohio. NCRM has 111 investigators from 40 different departments with over $37 million in NIH awards and is currently leading 31 regenerative medicine clinical trials to treat a number of diseases including cancer, orthopedics, cardiovascular and immunological disorders. More information on the NCRM can be found at www.ncrm.us.

About the National Center for Regenerative Medicine

The National Center for Regenerative Medicine (NCRM; www.ncrm.us) in Cleveland, OH., brings together researchers and physicians from Case Western Reserve University, the Cleveland Clinic and University Hospitals Case Medical Center. The NCRM provides a comprehensive approach, including basic through clinical as well as biomedical and tissue engineering research approaches, to develop new adult (non-embryonic) stem cell therapies for patients suffering from chronic and debilitating diseases including heart disease, cancer, genetic disorders, orthopedics, musculoskeletal and neurodegenerative diseases and injuries such as multiple sclerosis and spinal cord injury.

About the Cleveland Clinic

Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,500 full-time salaried physicians at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2005, there were 2.9 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were nearly 54,000 hospital admissions to Cleveland Clinic in 2005. Cleveland Clinic's Web site address is www.clevelandclinic.org.

About Case Western Reserve University

Case is among the nation's leading research institutions. Founded in 1826 and shaped by the unique merger of the Case Institute of Technology and Western Reserve University, Case is distinguished by its strengths in education, research, service, and experiential learning. Located in Cleveland, Case offers nationally recognized programs in the Arts and Sciences, Dental Medicine, Engineering, Law, Management, Medicine, Nursing, and Social Work. www.case.edu.