A Johns Hopkins engineer is trying to coax human stem cells
to turn into networks of new blood vessels that could
someday be used to replace damaged tissue in people with
heart disease, diabetes and other illnesses.
Sharon
Gerecht, an assistant professor of
chemical and
biomolecular engineering in the university's Whiting
School of Engineering, recently received a $150,000
two-year grant from the March of Dimes Foundation to
support this research; earlier, she received a $310,000
four-year award from the American Heart Association to
advance this promising line of study.
Gerecht is using the funds to answer important questions
about what happens at the molecular level when stem cells
differentiate: Which environmental cues cause them to form
blood vessels instead of other types of body tissue? Is it
a lack of oxygen? Is it the nutrients on which the cells
feed? Is it the texture and composition of the material on
which the cells are situated? And which type of stem cells
is best-suited to the assembly of replacement blood
vessels?
Solving these puzzles, Gerecht said, should help her and
other researchers to more effectively harness the power of
stem cells for human health remedies.
"Stem cell research has generated lots of excitement
because it has so much potential to help so many people who
are ill or injured," she said. "But we don't have a very
good understanding of what's going on when stem cells
change into a certain type of tissue, and we can't control
the transformation with much precision. We're trying to
learn more about what causes these cells to develop and
differentiate. With this knowledge in hand, we can make
medical applications involving stem cells more successful
and more reliable."
To look for these answers, Gerecht, recipient of the 2008
Maryland Outstanding Young Engineer Award, is using
engineering techniques to manipulate the environment in
which stem cells are placed. These lab experiments are
aimed at finding just the right molecular signals that will
cause stem cells to form blood vessel networks.
One of these environmental factors is the amount of oxygen
to which the stem cells are exposed. Reducing the oxygen
these cells require creates a condition called hypoxia. "We
are trying to mimic this condition in the lab," Gerecht
said, "because some research indicates that a lack of
oxygen causes stem cells to form blood vessels in order to
deliver more oxygenated blood to affected areas of the
body. We are using our engineering approach to find out if
this is actually what happens."
The research is important because the cardiovascular
network is one of the earliest differentiating and
functioning systems in human embryos. The March of Dimes
Foundation, which focuses on preventing birth defects,
premature births and infant mortality, awarded its grant to
Gerecht to study the role of hypoxia during vascular
development of human embryonic stem cells. The experiments
will be conducted with National Institutes of
Health-approved embryonic stem cell lines. Embryonic stem
cells can be made to reproduce in the lab with relative
ease, Gerecht said, but it is difficult to control the
differentiation of these blank-slate cells toward a
specific function, such as forming blood vessels.
With support from her American Heart Association grant, the
Johns Hopkins researcher is trying to determine if adult
stem cells are better candidates. It is easier, Gerecht
said, to direct certain adult stem cells to become the
building blocks of new blood vessels. They possess another
advantage: If the adult cells are taken from the patient
who will ultimately receive the treatment, tissue rejection
is unlikely. But adult stem cells have drawbacks as well:
They are more difficult to isolate and cannot easily be
made to multiply in the lab.
Gerecht also hopes to experiment with a third type that has
recently attracted attention — induced pluripotent
stem cells. These are adult cells that have been
reprogrammed through gene manipulation to behave more like
embryonic stem cells.
Major hurdles and years of additional research remain
before the replacement tissue Gerecht is trying to develop
may be used to restore healthy blood flow in humans. In
addition to selecting the right type of stem cells and the
proper growth environment, she must find the best way to
persuade the cells to form the proper three-dimensional
shape of living blood vessel networks. "To be able to do
that," she said, "we need to understand much more about the
underlying molecular events. Then, we can manipulate these
events to get the new blood vessels that we want."
To advance her research, Gerecht has been collaborating
with experts from elsewhere in the university, including
Gregg Semenza and Linzhao Cheng from the School of
Medicine's Institute
for Cell Engineering. She has also worked with Whiting
School of Engineering colleagues Denis Wirtz, a professor
of chemical and
biomolecular engineering, and Hai-Quan Mao, an
assistant professor of
materials science and engineering. Gerecht, Semenza,
Wirtz and Mao also are affiliated with the
Institute for
NanoBioTechnology at Johns Hopkins.
Gerecht earned her doctorate in biotechnology at the
Technion in Israel. She then continued her research in the
United States, spending three years as a postdoctoral
fellow at MIT. She joined the Johns Hopkins engineering
faculty in 2007.