The first clinical trial in the U.S. to test adult mesenchymal stem cells as a repair therapy after myocardial infarction has begun to enroll patients, according to a release from Johns Hopkins Heart Institute.

Previous research in animals showed that when adult stem cells were injected directly into the heart muscle, heart function was restored to its original condition within two months. Last November, at the American Heart Association Scientific Sessions 2004, the Hopkins team showed, again in animal studies, that more than 75 percent of dead scar tissue disappeared after therapy, which produced mostly healthy, normal-looking heart tissue and left only a small trace of the heart attack.

The Phase I study will involve 48 adults who have had their first myocardial infarction within 10 days of enrollment in the trial. All patients will have been stabilized before acceptance to the trial, and have undergone cardiac catheterization and ultrasound echocardiography to check that their main coronary vessels are clear of blockages that may precipitate another myocardial infarction. Eligible candidates must be between 21 and 85 years old, and have no pre-existing heart condition that has been treated or requires treatment during the study period.

Upon acceptance in the study, patients will be randomly assigned to one of four groups, each made up of 12 patients who will receive a preset dose of stem cell therapy or placebo. The study is double blinded, with neither researchers nor patients aware of who received stem cells until the Phase I study ends, six months after the last patient has enrolled.

After injecting stem cells taken from the bone marrow of an adult, human donor, into subjects’ bloodstream, the researchers will monitor the patient’s progress for two years to ensure that patients safely tolerated the infusion, determine any side effects and assess any differences in the three doses under study, each involving millions of adult stem cells. Initially, study participants will spend four days in the hospital, immediately after the procedure. The patients will then return for preset checkups, monthly for the first three months, and again after six months, 18 months and 24 months.

Magnetic resonance imaging studies, to show the size of the area of heart muscle scarred by the infarct and gauge the organ’s ability to pump, will be conducted at the beginning and end of the study as a measure of heart function. Conclusive results will only be available when and if Phase II and Phase III clinical trials proceed.

The Hopkins team expects that after injection, the adult stem cells will migrate to the damaged areas of the heart muscle, responding to chemical signals released by the heart after an infarct that triggers a repair response from the bone marrow.
Related clinical research under way in China also uses adult stem cells, but they come directly from the patient, and no universal donor is used as in the Hopkins study.

“This is an important milestone on the journey to better cardiovascular care and to realization of the promise of adult stem cell research,” said lead study investigator and cardiologist Joshua Hare, MD, professor of medicine at The Johns Hopkins University School of Medicine and its Heart Institute.

“Current approaches to cardiovascular disease can prevent heart attack or alleviate its after-effects, but they have not included repair of damage that leaves sizably dead portions of heart tissue as dangerous scars in the heart,” said study co-investigator and cardiologist Steven Schulman, MD.