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Swiss research team uses stem cell
‘cardiopatches’ to treat infarcted mice
05-08-2012
EDIT CONNECT
SHARING OPTIONS:
GENEVA, Switzerland—In the latest advancement in the field
of embryonic stem cell (ESC) research, a collaborating team of scientists from
Geneva University and the Ecole Polytechnique Federale de Lausanne (EPFL) has
successfully used ESC-based
"cardiopatches" to improve cardiac function in rats
that had induced heart attacks.
Publishing
their observations in the journal STEM CELLS Translational Medicine, the
scientists say their data provide evidence that stem cell-based cardiopatches
represent a promising therapeutic strategy to achieve efficient cell
implantation and improved global and regional cardiac function after myocardial
infarction.
Successful clinical use of stem cell transplantation has
proved challenging for
researchers across a wide spectrum of disciplines, as
clinical trials have produced mixed results for effective, safe delivery of
single-cell
suspensions of mesenchymal or satellite stem cells. In particular,
as noted by the scientists in their paper, aside from the choice of the right
cell
source for tissue regeneration, the optimal route for injection is still
fiercely debated, including the need for additional growth factors that may
favor or help tissue repair. Intravenous injection is relatively inefficient,
as only a very small percentage of the transplanted cells are found in
the
infarct region.
"To achieve substantial cardiac regeneration, one has to
provide a large
number of cells in a supportive microenvironment to maximize
cell retention, survival, differentiation into the appropriate cell type," they
point
out.
In recent years, researchers have attempted the generation
of complex, artificial
cardiovascular tissue constructs in vitro with characteristics close to the endogenous heart tissue
to be used as bioengineered cardiac grafts.
But although such in-vitro tissue engineering is a
valuable method to decipher the mechanisms of cardiac histogenesis, its
complexity may
represent an obstacle to electrical coupling with the diseased tissue,
and its cost tends to rule out large-scale clinical applications.
Alternatively, the researchers propose, one can rely on the
natural ability of stem cells to self-organize and
provide cardiac progenitors
together with a supportive matrix to achieve in-vitro or in-situ
tissue engineering. Several biomaterials
are currently used for cardiac tissue
engineering, such as fibrin, hyaluronic acid, collagen or polyethylene
glycol. In the current study, the
scientists used a fibrin
matrix that is a natural polymer, fully biocompatible and biodegradable and
capable of supporting cell growth, migration and
differentiation.
Cardiac-committed mouse ESCs were committed toward the
cardiac fate using a
protein growth factor called BMP2, then embedded into the
fibrin hydrogel. The cells were loaded
with superparamagnetic iron oxide nanoparticles
so they could be tracked using
magnetic resonance imaging, which also enabled the researchers to more
accurately assess regional and global heart
function.
The patches were then engrafted onto the hearts of
laboratory rats that had induced
heart attacks. Six weeks later, the hearts of
the animals receiving the mouse ESC-seeded patches showed significant
improvement over those receiving
patches loaded with iron oxide nanoparticles
alone. The patches had degraded, the cells had colonized the infarcted tissue
and new blood vessels were
forming in the vicinity of the transplanted patch.
Improvements reached beyond the part of the heart where the patch had been
applied to manifest
globally.
"We demonstrated that bone morphogenetic protein 2
(BMP2)-primed cardiac-committed
ESCs seeded into these fibrin patches
efficiently engraft and reduce remodeling and deterioration of cardiac functions
following myocardial
infarction," they concluded.
"Altogether, our data provide evidence that stem-cell based
cardiopatches represent a promising therapeutic strategy to achieve efficient
cell implantation and improved global and regional cardiac function after
myocardial infarction," says Dr. Marisa Jaconi of the Geneva University
Department of Pathology and Immunology and one of the study's authors.
Jaconi notes that "this was sort of a preliminary test to
see if we could improve engraftment—
whether we could use cardiac embryonic stem
cells without a purification procedure to see if engrafting the cells this way
and applying this type of
gel could obtain an effect immediately after creating
a myocardial infarction. This was, in essence, a preliminary work exercise of
style, if you will.
Now we have to think about how to secure these cells once
they are committed in bigger animal models, like sheep."
The work was supported in part by the Leenaards Foundation
and the Swiss
National
Code: E05081204 Back |
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