In human and animal studies, scientists at Johns
Hopkins have developed a fast and safe method for
collecting heart stem cells from remarkably small amounts
of biopsied heart tissue (15 mg or less), and growing the
cells in the lab to get more.
The technique gets the job done within four weeks,
producing enough stem cells to conceivably be used to
repair heart tissue clinically. The resulting clusters,
called cardiospheres, contain cells that retain the ability
to regenerate themselves and to develop into more
specialized heart cells that can conduct electrical
currents and contract like heart muscle should.
Their findings, if affirmed in further clinical
trials, could potentially offer patients a means of using
their own stem cells to repair heart tissue soon after they
have suffered a heart attack, or to regenerate weakened
muscle resulting from heart failure, perhaps averting the
need for heart transplants. By using a person's own adult
stem cells instead of those from another donor, there would
be no risk of triggering an immune response that could
Adult stem cells can be found in most living organ
tissue, such as the heart, and can generally develop into
related cell types, unlike embryonic stem cells that can
become any type of cell or tissue in the body.
"Harnessing the potential benefits of therapy with
adult stem cells is imperative if we are to make rapid
progress in treating heart disease. Cardiac stem cells,
grown from the heart itself, offer particular promise in
that they can regenerate beating heart muscle," said
Eduardo Marban, professor and chief of
cardiology at the Johns Hopkins School of Medicine and
its Heart Institute, and lead investigator of the study
presented Nov. 8 at the American Heart Association's
Scientific Sessions 2004. Marban is also director of the
Johns Hopkins Institute of Molecular Cardiobiology.
"Our basic research is trying to overcome the
biological problems in harnessing heart stem cells, so we
are very excited about our success in growing and analyzing
these cells," he said.
Using cardiac catheterization, where a tubelike probe
is inserted into a vein in the neck that links to the
heart, the Johns Hopkins team removed a small sample (15 mg
or less) of heart tissue from the right ventricle in 23
patients already undergoing treatment for heart failure.
Earlier studies in pigs found that adult stem cells were
most abundant in this region of the heart. Most other
researchers use invasive surgery to obtain larger portions
of muscle tissue, to increase the number of adult stem
cells harvested. An added benefit to catheterization is
that it can be performed quickly, in less than 20
The researchers then grew cells from the biopsy
tissues to isolate heart stem cells and reproduce them in
sufficient quantities, in excess of 100 million cells, that
most think would be suitable for therapy.
"Our biopsy method was very effective, and within four
weeks, most of the sample tissue produced enough heart stem
cells for more advanced clinical testing," added Marban,
who expanded this research at Johns Hopkins in June, based
on initial studies from the University of Rome in 2002. The
Rome team joined Johns Hopkins researchers in developing
the latest study.
The scientists also studied pig heart stem cells and
found that cardiospheres, when mixed with animal heart
tissue in growth solutions, developed new cells that were
able to conduct electricity and contract, two key
properties of healthy heart tissue and a key feature to any
potential long-term treatment of heart failure.
"Our next step is to test in animals whether these
cells can survive and work properly in cases of heart
attack and heart failure, using varying dose levels, while
also monitoring the electrophysiology in a living heart,"
The study was funded by the Donald W. Reynolds
Foundation. Other researchers who participated were Rachel
Ruckdeschel Smith, M. Roselle Abraham, Elisa Messina,
Alessandro Giacomello and Hee Cheol Cho.