Dataset Information

Functionally Improved Mesenchymal Stem Cells to Better Treat Myocardial Infarction.

ABSTRACT: Myocardial infarction (MI) is one of the leading causes of death worldwide. Mesenchymal stem cell (MSC) transplantation is considered a promising approach and has made significant progress in preclinical studies and clinical trials for treating MI. However, hurdles including poor survival, retention, homing, and differentiation capacity largely limit the therapeutic effect of transplanted MSCs. Many strategies such as preconditioning, genetic modification, cotransplantation with bioactive factors, and tissue engineering were developed to improve the survival and function of MSCs. On the other hand, optimizing the hostile transplantation microenvironment of the host myocardium is also of importance. Here, we review the modifications of MSCs as well as the host myocardium to improve the efficacy of MSC-based therapy against MI.

SUBMITTER: Chen Z

PROVIDER: S-EPMC6286742 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functionally Improved Mesenchymal Stem Cells to Better Treat Myocardial Infarction.

Chen Zhi Z Chen Long L Zeng Chunyu C Wang Wei Eric WE

Stem cells international 20181125

Myocardial infarction (MI) is one of the leading causes of death worldwide. Mesenchymal stem cell (MSC) transplantation is considered a promising approach and has made significant progress in preclinical studies and clinical trials for treating MI. However, hurdles including poor survival, retention, homing, and differentiation capacity largely limit the therapeutic effect of transplanted MSCs. Many strategies such as preconditioning, genetic modification, cotransplantation with bioactive factor ...[more]

PMID: 30622568

Similar Datasets

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

Functionally Improved Mesenchymal Stem Cells to Better Treat Myocardial Infarction.

Publications

Functionally Improved Mesenchymal Stem Cells to Better Treat Myocardial Infarction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets