Results from an animal study conducted at Johns
Hopkins show that stem cell therapy can be used effectively
to treat heart attacks, or myocardial infarcts, in pigs.
Stem cells taken from another pig's bone marrow, when
injected into the animal's damaged heart, were able to
restore the heart's function to its original condition.
If further animal studies and human clinical trials
prove equally successful, the Johns Hopkins researchers
believe this could be a new, widely applicable treatment to
repair and reverse the damage done to heart muscle that has
been infarcted, or destroyed, after losing its blood
supply. Nearly 8 million Americans alive today have
suffered at least one heart attack and so are at greater
risk for chronic heart failure or another, potentially
fatal, heart attack.
"Current treatments for cardiovascular disease prevent
heart attack from occurring and/or alleviate its
aftereffects, but they do not repair the damaged muscle
that results, leaving sizably dead portions of heart tissue
that lead to dangerous scars in the heart," said
cardiologist Joshua Hare, professor of medicine at Johns
Hopkins' School of Medicine and its
Heart Institute, and lead author of the study
presented Nov. 9 at the American Heart Association's
Scientific Sessions 2004.
"Damage done by a heart attack to heart muscle is
really the cause of all the serious complications of the
disease. Disturbances of heart rhythm can lead to sudden
cardiac death, and decreased muscle pumping function can
lead to congestive heart failure," said study co-author and
interventional cardiologist Alan Heldman, assistant
professor of medicine, who performed the injection
procedures. "Our aim is to find a way to repair the damage
done to the heart muscle and prevent these
complications."
In a controlled study of pigs (whose circulatory
systems are similar to humans'), seven received therapy and
another seven did not. The researchers found that
injections of bone marrow, or "adult" stem cells, directly
into heart muscle recently damaged by a heart attack
produced a nearly full recovery after a relatively short
period of time, two months.
Recovery was measured for the seven treated animals as
full restoration of heart muscle contraction to levels
existing prior to infarction. Indeed, dead scar tissue
nearly disappeared after therapy, which produced mostly
healthy, normal-looking heart tissue and left only a small
trace of the heart attack, the researchers said.
In contrast, in the seven animals in the control group
that did not receive therapy but were injected instead with
placebo, no recovery was observed, and the animals'
condition worsened, leading to the development of
congestive heart failure within two months after heart
attack.
In order to thoroughly cover the area of damaged heart
muscle — approximately the size of a one-dollar coin
— researchers gave every treated animal between 12
and 15 microscopic injections of adult stem cells, each
injection containing nearly 200 million cells.
The cells were injected directly into the heart muscle
using a specialized catheter inserted through a tiny
puncture in an artery, a procedure similar to other cardiac
catheterization techniques. Use of this catheterization
technique was shown to be safe and effective. Its use
increases the options for delivering stem cell therapy in
the future; most existing studies use intravenous
injections.
It remains unclear how or why the adult stem cells
developed into new and healthy heart tissue, or exactly how
long their healing effects last.
Adult stem cells were used because they are readily
available from the bone marrow, where they are plentiful. A
special kind of bone marrow stem cell, called a mesenchymal
stem cell, was separated from other kinds and used in this
study. While their precise biological action is not known,
mesenchymal bone marrrow stem cells are known to give rise
to a variety of cell types, including bone, cartilage, fat
and other kinds of connective tissue cells, such as those
in tendons, as well as muscle, such as the heart. A stem
cell is a special type of cell in the body from which all
others grow and derive into the major specialized cell
types of the body.
Using mesenchymal stem cells also avoided potential
problems with immunosuppression, in which each animal's
immune system might have attacked stem cells from sources
other than itself. Because they remain in an early stage of
development, mesenchymal stem cells do not trigger an
immune response, unlike what would happen if more developed
stem cells were used.
"While the bone marrow adult stem cells do not have
the same potential to develop into different organ tissues
as do embryonic stem cells, the use of adult stem cells in
this study shows their tremendous potential in developing
effective therapies for heart disease and avoids the
controversy surrounding destruction of embryos to obtain
the embryonic variety," Hare said.
"Among its many benefits are that adult stem cells are
readily available, meaning they can be extracted from the
patient, no donor is required, and the cells can be simply
reproduced if more are needed," he said. "In our animal
experiment, the treatment regimen was relatively simple,
requiring only injection to the damaged tissue. The therapy
was extremely effective, allowing for almost complete
recovery, with no serious complications, such as
immunosuppression, which is a problem in organ
transplantation. Now, we need to see how it works in
people."
According to the latest statistics from the American
Heart Association, in 2001 there were an estimated 565,000
new cases of heart attack in the United States, plus an
additional 300,000 cases of recurrent heart attack. Almost
185,000 of all heart attacks were fatal. The AHA also
estimated that 7.8 million Americans had suffered at least
one heart attack. People who have had a heart attack have a
sudden death rate that is four to six times greater than in
the general population. About two-thirds of heart attack
patients do not make a complete recovery; however, 88
percent of those under age 65 are able to return to
work.
This two-year study was funded by the
Johns
Hopkins Institute for Cell Engineering, the Donald W.
Reynolds Johns Hopkins Cardiovascular Center and the
National Institutes of Health. Further assistance came from
Osiris Therapeutics, which developed a process for
preparing mesenchymal stem cells and provided both funding
and the lines of adult stem cells used for each animal
involved in the study. Injection catheters were provided by
Biocardia Inc.
Other investigators in this research, conducted solely
at Johns Hopkins, were Luciano Amado, Marcus St. John,
Anastasios Saliaris, Jin-Sheng Xie, Stephen Cattaneo,
Daniel Durand, Torin Fitton, Jin Qiang Kuang, Garrick
Stewart, Jeff Brawn, Virginia Eneboe, Stephanie Lehrke,
William Baumgartner and Bradley Martin.