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Swiss research team uses stem cell ‘cardiopatches’ to treat infarcted mice
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."