The Effects of the Cardiac Extracellular Microenvironment on the Differentiation of Mesenchymal Stem Cells
Tang, Katherine Michele
2012
- Mesenchymal stem cell (MSC) cell therapy is a novel treatment for repairing and regenerating cardiac tissue post myocardial infarction (MI). Currently in human clinical trials, the therapy aims to repopulate the infarcted tissue with MSCs and prevent the negative remodeling process associated with MI. However, the treatments are limited by a lack of cell retention and differentiation to cardiomyocytes. ... read moreTherefore, this study aimed to determine how the extracellular microenvironment, including the composition and elasticity of the extracellular matrix (ECM) and oxygen content, affect the differentiation of MSCs. MSCs were grown on polyacrylamide gels, representing three physiologically relevant stiffnesses, combined with complete ECM composition or a single purified extracellular protein in order to study the effects of the ECM composition and stiffness on MSC differentiation. This method of differentiating MSCs was compared to the standard chemical method for cardiac differentiation: treatment with 5-azacytidine. Then, a disease model was developed to study how changes in stiffness, ECM composition, and oxygen content as a result of MI impact the differentiation of MSCs compared to a healthy cardiac environment. We found that the physiologically healthy stiffnesses tended to promote differentiation when combined with complete ECM. Furthermore, the disease model confirmed the results of the cell therapy clinical trials, where the healthy models better differentiated MSCs compared to the infarct model. However, it was also found that despite hypoxia being a result of MI, it promoted differentiation except when combined with infarct stiffness and infarct ECM composition. Based on these results, MSCs can be differentiated towards cardiomyocytes if given the appropriate environment, which can lead to improved methods of pre-differentiating MSCs prior to injection in cell therapy for more effective MI treatments.read less
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- k643bc16q
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- tufts:UA005.019.029.00001
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