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 were 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," said Eduardo Marban, senior author of both
studies and professor and chief of
cardiology at the 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," said study lead investigator Rachel
Ruckdeschel Smith, a biomedical engineering graduate
student. "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," said Lucio Barile, lead investigator of the study
and a cardiology research fellow at Johns 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 will examine how these cells perform in larger mammals,
such as pigs.
The studies were supported by the Donald W. Reynolds
Foundation. Co-authors were Elisa Messina, Michelle K.
Leppo, Hee Cheol Cho, M. Roselle Abraham, Mark Pittenger
and Alessandro Giacomello. Marban is also the Michel
Mirowski, M.D., Professor of Medicine at Johns Hopkins and
director of its Donald W. Reynolds Cardiovascular Clinical
Research Center and the Institute of Molecular
Cardiobiology.