What is Stem Cell: [StemCells] MORE hope for hearts!

Can Stem Cells Rescue Failing Hearts?
http://sciencenow.sciencemag.org/cgi/content/full/2007/1002/3
By Jennifer Couzin
ScienceNOW Daily News
2 October 2007
BETHESDA, MARYLAND--It's been more than 6 years since the first
person was injected with stem cells to rescue a failing heart.
Hundreds of patients have since followed the lead of that 46-year-
old German man. But experts are still divided on how well the
strategy works. At a 2-day symposium on cardiovascular regenerative
medicine at the National Institutes of Health here that ended today,
cardiologists, surgeons, pathologists, and other researchers debated
the future of cardiac cell therapy. Clinical trials and animal
studies are supplying a wealth of information; so far, the treatment
seems safe. But it is not at all clear which stem cells should be
given, or by what method--or, most importantly, whether patients who
get them are likelier to survive.

Cardiologists seized on cell therapy as a way to prevent decay of
heart muscle immediately after a heart attack and restore muscle
long after it had died. But three of the four largest clinical
trials have failed to accomplish what they set out to do--improve a
particular measure of heart function, measured as an increase the
amount of blood pumped, the so-called ejection fraction. By other
measures of health, however, such as regeneration of heart muscle or
preventing heart attacks, the trials may have been a success, argued
some of those who conducted them. "It's sad, but it's life" that the
trials failed, said Philippe Menasché, a cardiac surgeon at the
George Pompidou Hospital in Paris who has tried his hand at
transplanting skeletal muscle cells. But "should we be discouraged?
Certainly not."

One big problem, Menasché and others noted, is that the transplanted
cells may be disappearing quickly rather than sticking around to do
their job. Scientists have seen this happen in animals. Joshua Hare,
a cardiologist at the University of Miami in Coral Gables who also
directs the Interdisciplinary Stem Cell Institute, described work in
pigs showing a "washout of cells" within 8 weeks of delivery.
Charles Murry, a pathologist at the University of Washington,
Seattle, described how he spent a frustrating 18 months trying to
keep cardiac muscle cells derived from human embryonic stem cells
alive in mice after an induced heart attack. It nearly drove him
over the edge, he joked, showing a slide of a white pickup truck
hanging over a cliff. Finally, his lab found a cocktail of factors
that kept the cells alive, enabling them to engraft and preserve
cardiac function in affected mice. The work appeared in the
September issue of Nature Biotechnology.

A side effect could complicate how the cells are delivered.
Injecting cells directly into the heart, which facilitates
engraftment, may cause arrhythmias. In a sobering talk in which he
chided researchers for moving quickly into human trials before
conducting exhaustive studies in large animals, Menasché pointed to
a study published in May in Circulation by a team in Britain,
showing that rats suffered more arrhythmias if bone marrow was shot
straight into the heart. (Menasché's own cell therapy trial was
plagued by several cases of arrhythmias, which he now is not certain
were a result of the cell therapy.)

Another hot question: Can injected cells develop in ways that
ameliorate heart disease? Scientists are working with a hodgepodge
of various stem cells, some better characterized than others. They
include Hare's favored mesenchymal stem cells, which can become
bone, muscle, and more; a cocktail of bone marrow cells used in
German trials; and bone marrow cells that express a certain marker
on their surface called CD34. One trial in the planning stages,
based in Cedars-Sinai Medical Center in Los Angeles, California, and
at Johns Hopkins University in Baltimore, Maryland, hopes to use a
natural pool of cardiac stem cells, whereas groups such as Murry's
are interested in coaxing embryonic stem cells into more defined but
still flexible heart cells. Pinpointing what each of these cell
types can accomplish in an animal isn't easy. "Right now, we're
limited to throwing them on plastic" to see what they do, said David
Scadden, co-director of Harvard's Stem Cell Institute in Cambridge,
Massachusetts, in a talk.

Potency of stem cells is also an issue. Cardiologist Douglas Losordo
of Northwestern University in Chicago, Illinois, reviewed published
studies showing that certain stem cells, such as those from bone
marrow, may be less potent when they come from a heart patient than
from a healthy person. Menasché speculates that conditions such as
diabetes or atherosclerosis can impair function of some bone marrow
stem cells. Using cells from patients--most of what's been tried so
far--has other downsides, such as cost and complexity. Hare
described the first-ever trial in heart patients to take a different
tack and use donor stem cells. Led by Hare and sponsored by Osiris
Therapeutics in Baltimore, the trial enrolled 53 people who got
mesenchymal stem cells within 10 days of a heart attack. In the
spring, Hare reported that there were no significant safety
problems, such as mesenchymal stem cells developing into other
organs.

What next? One of the biggest cell therapy enthusiasts, Andreas
Zeiher of the University of Frankfurt, Germany, said that "it's time
to embark on a 1000 person clinical trial" to nail down once and for
all whether cell therapy keeps heart patients alive and in better
health--a question the trials so far have been too small to answer.
The circulatory diseases targeted by cardiac cell therapy continue
to expand: Losordo hopes to launch a trial in critical limb
ischemia, which affects diabetes patients and others and often
results in amputation and even death. Researchers are mindful, too,
that cardiac patients are desperate for new treatments. Some are
flocking to Thailand, where a company now offers cardiac cell
therapy--at a steep cost.

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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