Stem cells derived from human heart tissue develop into multicellular, spherical structures called cardiospheres that express the normal properties of primitive heart tissue, smooth muscle and blood vessel cells, according to a study by Johns Hopkins researchers.
In a related study, cells grown in the laboratory from these cardiospheres and injected into the hearts of mice following a lab-induced heart attack migrated straight to damaged tissue and regenerated, improving the organ's ability to pump blood throughout the animal's body.
Results from both studies are to be presented Nov. 14 at the American Heart Association's annual Scientific Sessions in Dallas.
"The findings could potentially offer patients use of their own stem cells to repair heart tissue soon after a heart attack, or to regenerate weakened muscle resulting from heart failure, perhaps averting the need for heart transplants," says Eduardo Marbán, M.D., Ph.D., senior author of both studies and professor and chief of cardiology at The Johns Hopkins University School of Medicine and its Heart Institute. "By using a patient's own adult stem cells rather than a donor's, there would be no risk of triggering an immune response that could cause rejection."
In the first study, researchers took heart tissue samples from 10 patients age 20 to 80 who had recently received a heart transplant, and as part of their regular checkup to make sure the new heart was functioning properly. Researchers grew these tissues for two weeks, collecting any cardiac stem cells that started to migrate out, and then grew those loose cells with growth chemicals until they formed cardiospheres. After two weeks of growth, the cardiospheres organized into structures consisting of at least two distinct, partially overlapping layers of cells. Cells in the center of the cluster had properties most like cardiac stem cells, while cells on the surface had properties similar either to myocytes (heart muscle cells with the ability to contract) or to cells that could develop into smooth muscle or blood vessel lining.
"We don't know yet the purpose or advantages of this organization," says study lead investigator Rachel Ruckdeschel Smith, a biomedical engineering graduate student at Hopkins. "Cardiospheres represent an interesting model of early, test-tube heart cell development. They expressed common characteristics of other cells while retaining a unique appearance."
In the second study, the research team grew adult heart tissue samples to extract cardiac stem cells, which were then grown to create cardiosphere-derived cells. Researchers induced heart attacks in 19 mice, injecting eight with the cells grown from cardiospheres, in doses of approximately 100,000 cells, while other mice were injected with fibroblast placebo cells. The injections were made directly into the area bordering the site of the heart attack, located in the left ventricle, the heart's main pumping chamber. They then measured the infusion and migration of the cells at zero, eight and 20 days following injection to see what would happen.
At day zero, cells were located at injection sites bordering the heart attack area, but at days eight and 20, cells were mainly distributed within the area damaged by heart attack.
Researchers also studied the cells' function by injecting the mouse hearts with either cardiosphere-derived cells, human skin cells or placebo cells 20 days after heart attack, then using ultrasound echocardiography to measure the ability of the hearts to pump blood throughout the body. The hearts treated with cardiosphere-derived cells performed an average of 15 percent to 20 percent better than those treated with either of the controls.
"It was remarkable to see this improvement after only 20 days," says Lucio Barile, M.D., lead investigator of the study and a cardiology research fellow at Hopkins. "Human cardiosphere-derived cells migrated into the heart attack zone, partially replaced the scar and improved the heart's function."
Further studies will look at the behavior of injected cardiosphere-derived cells over a longer period of time, and to examine how these cells perform in larger mammals, such as pigs.
The studies were supported by the Donald W. Reynolds Foundation. Coauthors were Elisa Messina, M.D.; Michelle K. Leppo; Hee Cheol Cho, Ph.D.; M. Roselle Abraham, M.D.; Mark Pittenger, Ph.D., and Alessandro Giacomello, M.D. Marbán is also the Michel Mirowski, M.D., Professor of Medicine at Hopkins and director of its Donald W. Reynolds Cardiovascular Clinical Research Center and the Institute of Molecular Cardiobiology.