CLINICAL
NEWS
American College of Cardiology Extended Learning
ACCEL interviews and topical summaries of cardiology’s
most interesting research areas
Regenerative Therapy: Stem Cells Generate More Interest
W
e’re all developmental products of stem
cells. Apart from the billions of cells
generated after sperm meets egg, each of
us also has an elegant “rescue” system of stem cells
circulating in the blood and residing in our organs. A
better understanding of this system is already leading to enhanced repair processes locally after injury.
However, the research is going well beyond using stem cells or genes to activate the body’s native
repair function to facilitate the repair or recovery
of any damaged or dysfunctional organs, tissues,
or vessels. Down the road, these efforts may lead
to the regeneration or repair of whole hearts or
other organs (see this issue’s cover story). Where
we currently are on this particular research highway might surprise you.
Cell therapy remains the biggest and fastest-growing segment of the regenerative medicine industry.
More than $5 billion has been invested, so far, with
more than 2,500 regenerative medicine clinical trials
in progress (Frost & Sullivan, 2015). Globally, the
stem cell therapy market is expected to be worth
$40 billion by 2020 and $180 billion by 2030.
Some investigators have moved from academia
to industry, partly because industry—including big
pharma—has become expanding their regenerative
medicine investment, including Pfizer, Novartis,
Cellectis (France), Celgene, Teva Pharma, and
Johnson & Johnson. Not all are focusing on cardiovascular applications, of course, although Teva is
a major partner in the Chronic Congestive Heart
Failure program (phase III trials) and J&J is investing up to $325 million (depending on milestone
attainment) in a stem cell therapy for cardiovascular disease (phase II trials scheduled).
Leslie Miller, MD, has been chair of the Department of Cardiovascular Medicine at the University
of Minnesota, Minneapolis, MN, and was most
recently at the University of South Florida (USF),
Tampa, FL, where he directed the cardiovascular
clinical research program. He has also been director of cardiology at Washington Hospital Center,
Georgetown University Hospital, and Georgetown
University School of Medicine.
Today, he is the chief science officer of Okyanos Cell Therapy and his focus is now entirely on
regenerative medicine and the use of adult stem
cells to repair and recover heart function. He is one
of four editors responsible for the new textbook
(September 2015), Stem Cell and Gene Therapy for
Cardiovascular Disease.1
TURNING THE CORNER?
You may be more familiar with the failures—let’s call
them setbacks—in this field in recent years, but the
reality is far more positive. The goal of using stem
ACC.org/CSWN
cell and gene therapy to enhance tissue repair of
acute and chronic disease and create new treatments
to reduce the significant morbidity and mortality
from cardiovascular disease (CVD) has come a long
way in the last decade. The field of regenerative
medicine is an excellent example of the bidirectional
flow of translational medicine between the basic and
clinical sciences. Shortcomings in clinical trials have
driven a good deal of basic research, which has led
to further understanding of important mechanisms,
such as cell homing and viability.
Here’s a good example: the National Institutes
of Health FOCUS trial of 92 patients with stable
ischemic heart failure (HF; a median left ventricular
ejection fraction [LVEF] of 27%) randomized 2:1 to
autologous bone marrow cells or placebo. About 100
million cells were delivered in the active therapy arm
via endocardial cell delivery (the NOGA catheter).
There was no change in various parameters until
they looked at one variable: age. Patients older than
62 years had 0% change in LVEF, while those who
were younger had a 4.7% increase in LVEF.
[T]he human rescue
system of stem cells is
often unable to repair
damaged hearts in those
for whom the repair is
most often needed.
It turns out that one major limitation is that human stem cells become dysfunctional with age. They
become less able or even unable to replicate and the
age at which this happens appears to be around 60
years. Similarly, the number and effectiveness of
bone marrow-derived and circulating stem cells are
also reduced in patients with severe disease or many
risk factors for CVD. Therefore, notwithstanding its
elegance, the human rescue system of stem cells is
often unable to repair damaged hearts in those for
whom repair is most often needed.
Not too long ago, it was thought that any allogenic (read: foreign) cell was thought to require longterm immunosuppression. It turns out that mesenchymal stem cells seem to be “immune privileged,”
meaning minimal alloimmune (antibody) response.
Other cells have also been found to be as effective
as autologous cells, meaning it may be possible to
develop off-the-shelf therapy for any age, or need
using, for example, mesenchymal stem cells from
youthful donors to treat aging individuals with CVD.
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