Untitled - Interdisciplinary Stem Cell Institute - University of Miami

In its bone and skin division, associate
professor of dermatology Evangelos
Badiavas is using cells that have been
expanded and optimized at ISCI’s Cell
Manufacturing Laboratory to continue
the groundbreaking work he began ten
years ago at Brown University.
“We were the first with the idea
of taking a stem cell population and
putting it into a chronic wound,” says
Badiavas, director of ISCI’s Laboratory
on Cutaneous Wound Healing and
Regeneration. He and his team at
Brown applied bone marrow cells topically
to a surgical wound that had been
open for several years. The cells rebuilt
skin tissue, healing thoroughly rather
than simply scarring.
“It was one of those worth-it
moments—all those nights in the lab,
my wife being angry with me for being
home late,” Badiavas recalls. “It’s a situation
where you made a difference with
your own hands, your own ideas.”
Since arriving at ISCI in 2008,
Badiavas, who did his residency and
fellowship at the Miller School, has
had several “worth-it” moments. He
describes one patient with bilateral leg
ulcers from severe veinous disease who
was dependent on narcotics for pain
management. Injection of the patient’s
own bone marrow cells closed his
wounds, restored his ability to walk,
and got him off of narcotics.
Mesenchymal cells show
widespread therapeutic
promise because of their
ability to fly under the immune system’s
radar. But they alone cannot regenerate
blood destroyed by chemotherapy
or radiation treatment for cancer or
other diseases. Hematapoietic (bloodforming)
cells from healthy donors are
necessary, but they introduce a serious
rejection risk called graft-versus-host
Through their work with stem cells, Evangelos Badiavas, associate professor of dermatology and cutaneous surgery, and research
associate Marcela Salgado have been able to close chronic wounds and restore patients’ independence and quality of life.
disease, even when the donor is a close
HLA match.
“We can always shut down graftversus-host
disease with steroids or other
lines of immunosuppressants,” explains
Krishna Komanduri, the Kalish Family
Endowed Chair in Stem Cell Transplantation
and director of the UM/Sylvester
Stem Cell Transplant Program. “But the
problem is that patients end up so profoundly
immunodeficient they often
die of infection.”
Komanduri’s lab at ISCI is working
on ways to prevent graft-versus-host
disease while reducing risk of infection
and relapse. A lot of his work is with
T cells, components of the human immune
system also vulnerable to HIV.
“In many cases, the same pathogens
that cause problems in HIV-infected patients
also cause problems in bone marrow
transplant patients,” says Komanduri,
who first worked with T cells in the
early 1990s at an HIV immunology lab
in San Francisco, the epicenter of the
AIDS epidemic at that time.
When chemotherapy destroys leukemia
cells, it takes T cells with it. Hematopoietic
stem cell transplants also deliver
new T cells from the donor, but they
take time to multiply, leaving the patient
vulnerable to infection. When infectionfighting
T cells finally repopulate, they
introduce the potential for graft-versushost
disease.
It turns out that not all T cells are
created equal: Some can cause graftversus-host
disease, and some can
reverse it. Komanduri developed a
novel technique, called flow cytometry,
that helps isolate different types of
T cells. His team is working on a transplant
protocol that combines these different
T cells in a ratio that can quash
infections and graft-versus-host disease
at the same time.
Komanduri is also exploring how
to improve outcomes in blood cancer
patients who can’t find a donor match.
Cord blood transplants use stem
cells from the small amount of blood
that’s in a baby’s umbilical cord and
placenta, usually discarded after birth.
This blood contains hematapoietic
stem cells, along with immature T cells
that are less likely to cause graft-versushost
disease. Therefore, they can be
used even when they’re not a perfect
HLA match. Komanduri is testing a
new way of growing cord blood cells
on a “feeder” layer of mesenchymal
cells to boost immune recovery after
transplant.
Over the last 20 years, both private
and public cord banks have sprouted
up worldwide. Public banks accept
donations for anyone in need. Private
banks charge a fee to store cord blood
solely for use by the family that deposited
it.
While a federal funding ban on research
involving embryonic stem cells
(those derived from an unused embryo
created through in vitro fertilization)
was lifted in 2009, ISCI trials don’t currently
involve this category of stem cell.
Hare notes that only mesenchymal cells
are used in clinical trials presently under
way at ISCI, but several research teams
are shifting focus to a new area—tissuespecific
stem cells.
“What’s driving progress in the field
is the discovery that every organ has its
own specific stem cell,” Hare explains.
“We’re working very intently now on
cardiac stem cells, and we know from
animal studies that these cells are more
potent than mesenchymal cells.”
He says this discovery, which happened
within the past ten years, is one
example of how quickly the science of
translational medicine is moving. He
also gives props to patients like Deborah
Wilson, who are eager to participate in
the trials.
“If I look back on the last ten years,
I never thought we’d be this far along,”
Hare admits. “I think this is ready for
approval, at least in its first iteration,
by 2015. It doesn’t mean we won’t
improve on it. We didn’t avoid using
penicillin because we were waiting for
the third-generation antibiotics. We
used what we had at the time that we
knew worked. And we’ll do the same
with stem cell therapies.”
In April ISCI hosted an appreciation
luncheon that drew more than 50
clinical trial participants, one of whom
showed his appreciation and energy
level by giving a spontaneous breakdancing
performance during the event.
“They are seeking us out from all
over the country,” Hare says of his
patients. “They understand that we
don’t know whether it’s going to work,
but they stand shoulder to shoulder
with us in the importance of doing this
research.”
meredith danton camel is an
editorial director at the University of Miami.
For more on clinical trials and stem cell
research at ISCI, visit http://isci.med.miami.edu.
To watch UHealth’s Suncoast Emmy Awardwinning
episode of Breakthrough Medicine,
“Stem Cell Therapy: Healing Force of the Future,”
go to www.uhealthsystem.com/breakthrough/
episode4.asp.
MoreCutting-EdgeActivityatISCI
t
Nanette H. Bishopric, recipient of the American College of Cardiology’s 2010
Distinguished Scientist Award, professor of medicine, and director of the Cardiovascular
Genetics Laboratory, led a team of researchers in discovering a factor that can
serve as a predictor of stem cell development into blood vessels, a key finding for
future applications.
t David Seo, director of the Genomic Medicine Registry and associate professor
of medicine, Division of Cardiology, is exploring the use of bone marrow-derived
stem cells to repair artherosclerosis.
t Omaida Velazquez, vice chair of research surgery and David Kimmelman
Endowed Chair of Vascular and Endovascular Surgery, is principal investigator of an
National Institutes of Health-funded grant to study growth factors critical to the
wound-healing process, among several other stem cell-related studies she is leading.
t Karen Young, assistant professor of clinical pediatrics, Division of Neonatology,
is studying how stem cells become lung cells. She received the 2010 Micah
Batchelor Award for Excellence in Children’s Health Research and a $300,000 grant
for research that aims to identify factors leading to impaired lung cell development
in premature infants.
18 Miami magazine Fall 2011 Fall 2011 Miami magazine 19