Download Mend a broken heart - Adam J. Engler

Mend a broken heart
News from
The American Society
for Cell Biology
49th Annual Meeting
San Diego, CA
December 5–9, 2009
EMBARGOED
FOR RELEASE
10:00 am, U.S. Pacific Time
Tuesday, December 8, 2009
Contact
Jennifer L. Young
University of California,
San Diego
251 Powell-Focht Bioengineering Hall
9500 Gilman Dr., M/C 0412
La Jolla, CA 92093
[email protected]
Author presents
Tuesday, December 8, 2009
12:30–2:00 pm
Poster Session 3:
Extracellular Matrix and
Morphogenesis
Program 2003
Board B382
Exhibit Halls D–H
Engineered “Smart” Materials
for Improved Cardiomyocyte
Differentiation
J.L. Young, A.J. Engler
Bioengineering, University of
California, San Diego, La Jolla,
CA
A framework of “smart” materials
mimics the elasticity of the matrix
that surrounds stem cells, helping
to develop new cardiac muscle to
repair damaged hearts
A
novel technique of growing stem
cells on a “smart” material framework that supports the development of cardiac muscle cells may open
the way for new treatments to regenerate
damaged hearts.
Jennifer L. Young and Adam J. Engler
of the Jacobs School of Engineering at the
University of California, San Diego, grew
adult precardiac stem cells on a hyaluronic acid scaffold that is chemically designed
to change its stiffness over time, just as
developmental cues stiffen the extracellular matrix (ECM), a three-dimensional
protein scaffold of collagen, fibronectin,
and other materials that surrounds cells.
This stiffening molds embryonic stem
cells into functioning cardiomyocytes in
the body.
Young and Engler used atomic force
microscopy measurements of elasticity as
benchmarks to “tune” their elastic material so that it would polymerize over time,
growing stiffer through cross-linking and
squeezing stem cells in the way that the
ECM shapes maturing heart muscle cells
in the developing embryo. The new technique, say the researchers, better produces newly differentiated cardiomyocytes than conventional techniques. The
combination of these cells and materials
could replace heart muscle tissue badly
damaged by heart attacks or other forms
of cardiac disease.
Heart disease is still the leading cause
of death in the U.S., killing 631,636 Americans in 2006, according to the Centers
for Disease Control and Prevention. Until
the discovery of adult stem cells in nearly
all tissues, cardiologists were taught that
damaged heart muscle cells could not
regenerate. Stem cell therapy seemed a
way around that old dogma, yet previous
attempts to place adult stem cells directly
into damaged heart muscle failed, according to Young.
Called cellular cardiomyoplasty, these
unsuccessful experimental stem cell trials
injected stem cells directly into damaged heart muscle with the expectation
that they would differentiate into cardiac
cells with the ability to regenerate healthy
cardiac muscle and restore cardiac function. Instead, the injected stem cells took
their cue from the stiff, scarred cardiac
muscle wall that they were supposed to
reinforce. Heart wall stiffness only slightly
decreased and cardiac function improved
only marginally. It’s now thought that
the needle used to inject the stem cells
actually poked holes into scarred heart
muscle, making it slightly softer instead of
regenerating the tissue. Worse, the stem
cells themselves formed small, calcified
lesions: They were instead directed by the
scarred muscle to mature into bonelike
cells.
In the UCSD experiment, researchers grew stem cells on a framework engineered to mimic the changing elastic
properties of the ECM during development and then stained the cells for proteins that mark cardiogenesis. The results
are encouraging, says Young. “By tuning
this material to mimic in situ timedependent stiffness changes, [we found
that] cells placed in this material indicate
improved cardiac differentiation.” She
believes that subsequent studies in animal models could hone the technique to
be extremely therapeutically beneficial.
The researchers believe that using “smart”
materials to tune stem cells for therapeutic effects will shape the future treatment
of cardiovascular disease.
VIDEO at:
https://www.ascb.org/
ascbsec/press/embargo/
A
10
B
The
Ameri can
Previous attempts at “cardiomyoplasty” with stem cells failed.
A) Image of a cross-section of the
heart muscle wall post-heart attack.
The lack of muscle cells (red) and
presence of a scar (blue) indicate the
damage that occurs to the muscle.
(B) Similar cross-section of the heart
muscle wall post-heart attack, from
an animal treated with 106 adult stem
cells. Despite a modest increase in
cells (red), much of the cross-section
is still scar tissue, indicating that
stem cells alone are not sufficient to
remodel the scar and restore function.
s o ci ety
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Cell
Bi o lo gy