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Therapeutic Use of Stem Cells for Myocardial Infarction.

ABSTRACT: Myocardial infarction is a leading cause of morbidity and mortality worldwide. Although medical and surgical treatments can significantly improve patient outcomes, no treatment currently available is able to generate new contractile tissue or reverse ischemic myocardium. Driven by the recent/novel understanding that regenerative processes do exist in the myocardium-tissue previously thought not to possess regenerative properties-the use of stem cells has emerged as a promising therapeutic approach with high expectations. The literature describes the use of cells from various sources, categorizing them as either embryonic, induced pluripotent, or adult/tissue stem cells (mesenchymal, hematopoietic, skeletal myoblasts, cardiac stem cells). Many publications show the successful use of these cells to regenerate damaged myocardium in both animal and human models; however, more studies are needed to directly compare cells of various origins in efforts to draw conclusions on the ideal source. Although numerous challenges exist in this developing area of research and clinical practice, prospects are encouraging. The following aims to provide a concise review outlining the different types of stem cells used in patients after myocardial infarction.

SUBMITTER: Madigan M

PROVIDER: S-EPMC6027340 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Therapeutic Use of Stem Cells for Myocardial Infarction.

Madigan Mariah M Atoui Rony R

Bioengineering (Basel, Switzerland) 20180406 2

Myocardial infarction is a leading cause of morbidity and mortality worldwide. Although medical and surgical treatments can significantly improve patient outcomes, no treatment currently available is able to generate new contractile tissue or reverse ischemic myocardium. Driven by the recent/novel understanding that regenerative processes do exist in the myocardium-tissue previously thought not to possess regenerative properties-the use of stem cells has emerged as a promising therapeutic approa ...[more]

PMID: 29642402

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Project description:IntroductionAlthough 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.MethodsMechanical 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.ResultsThe 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.ConclusionsThis 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.

Dataset Information

Therapeutic Use of Stem Cells for Myocardial Infarction.

Publications

Therapeutic Use of Stem Cells for Myocardial Infarction.

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