| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Sullivan, Kelly Elizabeth Quinn, Kyle Patrick Tang, Katherine Michele Georgakoudi, Irene Black, Lauren Deems |
| Abstract | Introduction Although stem cell therapy is a promising treatment for myocardial infarction, the minimal functional improvements observed clinically limit its widespread application. A need exists to maximize the therapeutic potential of these stem cells by first understanding what factors within the infarct microenvironment affect their ability to regenerate the necrotic tissue. In this study, we assessed both differentiation capacity and paracrine signaling as a function of extracellular matrix remodeling after myocardial infarction. Methods Mechanical and compositional changes to the decellularized infarcted myocardium were characterized to understand how the extracellular environment, specifically, was altered as a function of time after coronary artery ligation in Sprague–Dawley rats. These alterations were first modeled in a polyacrylamide gel system to understand how the variables of composition and stiffness drive mesenchymal stem cell differentiation towards a cardiac lineage. Finally, the paracrine secretome was characterized as a function of matrix remodeling through gene and protein expression and conditioned media studies. Results The decellularized infarct tissue revealed significant alterations in both the mechanical and compositional properties of the ECM with remodeling following infarction. This altered microenvironment dynamically regulates the potential for early cardiac differentiation. Whereas Nkx2.5 expression is limited in the presence of chronic remodeled matrix of increased stiffness, GATA4 expression is enhanced. In addition, the remodeled matrix promotes the expression of several proangiogenic, prosurvival, antifibrotic, and immunomodulatory growth factors. In particular, an increase in HGF and SDF1 expression and secretion by mesenchymal stem cells can rescue oxidatively stressed cardiomyocytes in vitro. Conclusions This study demonstrated that decellularization of diseased tissue allows for the exclusive analysis of the remodeled matrix and its ability to influence significantly the cellular phenotype. Characterization of cell fate as a function of myocardial remodeling following infarction is critical in developing the ideal strategy for cell implantation to maximize tissue regeneration and to ultimately reduce the prevalence and severity of heart failure. |
| Related Links | https://stemcellres.biomedcentral.com/counter/pdf/10.1186/scrt403.pdf |
| Ending Page | 16 |
| Page Count | 16 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17576512 |
| DOI | 10.1186/scrt403 |
| Journal | Stem Cell Research & Therapy |
| Issue Number | 1 |
| Volume Number | 5 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2014-01-24 |
| Access Restriction | Open |
| Subject Keyword | Stem Cells Cell Biology Regenerative Medicine Tissue Engineering Biomedical Engineering and Bioengineering Second Harmonic Generation Paracrine Signaling Infarcted Heart Cardiac Differentiation GATA4 Expression Regenerative Medicine/Tissue Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Biochemistry, Genetics and Molecular Biology Molecular Medicine |
| Journal Impact Factor | 7.1/2023 |
| 5-Year Journal Impact Factor | 7.9/2023 |
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