title: Recovery of cardiac function mediated by MSC and interleukin-10 plasmid functionalised scaffold.
abstract: Stem cell transplantation has been suggested as a treatment for myocardial infarction, but clinical studies have yet to demonstrate conclusive, positive effects. This may be related to poor survival of the transplanted stem cells due to the inflammatory response following myocardial infarction. To address this, a scaffold-based stem cell delivery system was functionalised with anti-inflammatory plasmids (interleukin-10) to improve stem cell retention and recovery of cardiac function. Myocardial infarction was induced and these functionalised scaffolds were applied over the infarcted myocardium. Four weeks later, stem cell retention, cardiac function, remodelling and inflammation were quantified. Interleukin-10 gene transfer improved stem cell retention by more than five-fold and the hearts treated with scaffold, stem cells and interleukin-10 had significant functional recovery compared to the scaffold control (scaffold: -10 ± 7%, scaffold, interleukin-10 and stem cells: +7 ± 6%). This improved function was associated with increased infarcted wall thickness and increased ratios of collagen type III/type I, decreased cell death, and a change in macrophage markers from mainly cytotoxic in the scaffold group to mainly regulatory in scaffold, stem cells and interleukin-10 group. Thus, treatment of myocardial infarction with stem cells and interleukin-10 gene transfer significantly improved stem cell retention and ultimately improved overall cardiac function.
authors.affiliation: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Holladay
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Duffy
authors.forename: Xizhe
authors.initials: X
authors.lastname: Chen
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sefton
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Brien
authors.forename: Abhay S
authors.initials: AS
authors.lastname: Pandit
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009203:Myocardial Infarction / Q000473:pathology; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000502:physiology*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D016753:Interleukin-10