Publishing their observations in the journal STEM CELLS Translational Medicine, thescientists say their data provide evidence that stem cell-based cardiopatchesrepresent a promising therapeutic strategy to achieve efficient cellimplantation and improved global and regional cardiac function after myocardialinfarction.
Successful clinical use of stem cell transplantation hasproved challenging for researchers across a wide spectrum of disciplines, asclinical trials have produced mixed results for effective, safe delivery ofsingle-cell suspensions of mesenchymal or satellite stem cells. In particular,as noted by the scientists in their paper, aside from the choice of the rightcell source for tissue regeneration, the optimal route for injection is stillfiercely debated, including the need for additional growth factors that mayfavor or help tissue repair. Intravenous injection is relatively inefficient,as only a very small percentage of the transplanted cells are found in theinfarct region.
"To achieve substantial cardiac regeneration, one has toprovide a large number of cells in a supportive microenvironment to maximizecell retention, survival, differentiation into the appropriate cell type," theypoint out.
In recent years, researchers have attempted the generationof complex, artificial cardiovascular tissue constructs in vitro with characteristics close to the endogenous heart tissueto be used as bioengineered cardiac grafts. But although such in-vitro tissue engineering is avaluable method to decipher the mechanisms of cardiac histogenesis, itscomplexity 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 thenatural ability of stem cells to self-organize and provide cardiac progenitorstogether with a supportive matrix to achieve in-vitro or in-situtissue engineering. Several biomaterials are currently used for cardiac tissueengineering, such as fibrin, hyaluronic acid, collagen or polyethylene
glycol. In the current study, the scientists used a fibrinmatrix that is a natural polymer, fully biocompatible and biodegradable andcapable of supporting cell growth, migration and differentiation.
Cardiac-committed mouse ESCs were committed toward thecardiac fate using a protein growth factor called BMP2, then embedded into thefibrin hydrogel. The cells were loadedwith superparamagnetic iron oxide nanoparticles so they could be tracked usingmagnetic resonance imaging, which also enabled the researchers to moreaccurately assess regional and global heart function.
The patches were then engrafted onto the hearts oflaboratory rats that had induced heart attacks. Six weeks later, the hearts ofthe animals receiving the mouse ESC-seeded patches showed significantimprovement over those receiving patches loaded with iron oxide nanoparticlesalone. The patches had degraded, the cells had colonized the infarcted tissueand new blood vessels were forming in the vicinity of the transplanted patch.Improvements reached beyond the part of the heart where the patch had beenapplied to manifest globally.
"We demonstrated that bone morphogenetic protein 2(BMP2)-primed cardiac-committed ESCs seeded into these fibrin patchesefficiently engraft and reduce remodeling and deterioration of cardiac functionsfollowing myocardial infarction," they concluded.
"Altogether, our data provide evidence that stem-cell basedcardiopatches represent a promising therapeutic strategy to achieve efficientcell implantation and improved global and regional cardiac function aftermyocardial infarction," says Dr. Marisa Jaconi of the Geneva UniversityDepartment of Pathology and Immunology and one of the study's authors.
Jaconi notes that "this was sort of a preliminary test tosee if we could improve engraftment—whether we could use cardiac embryonic stemcells without a purification procedure to see if engrafting the cells this wayand applying this type of gel could obtain an effect immediately after creatinga myocardial infarction. This was, in essence, a preliminary work exercise ofstyle, if you will. Now we have to think about how to secure these cells oncethey are committed in bigger animal models, like sheep."
The work was supported in part by the Leenaards Foundationand the Swiss National
