The role of miR‐301a and the influence of extracellular environment surface tensions on the dichotomous phenotype shown in primary human bone marrow‐derived mesenchymal stem cells (868.4)

It has been established that the microenvironment of mesenchymal stem cells (MSCs) is influential in determining differentiation. Expression of non‐coding RNAs, such as microRNAs, has been found to be altered in response to various stimuli and may thus contribute to stem cell differentiation. Previous research in our lab has shown that miR‐301a mediates a dichotomous phenotype in primary human MSCs. As MSCs have been found to directly contribute to cardiac remodeling post‐MI, we sought to understand how migration from bone marrow to cardiac tissue could influence MSC differentiation. The objective of this study is to analyze how varying matrix stiffness would influence miR‐301a expression and MSC differentiation. We analyzed mRNA levels of c‐kit, Dicer, MYH9 and 10 and found that these have increased expression on fibronectin‐coated 2kPa plates simulating native bone marrow stiffness, however this is blunted on 15kPa plates, simulating left ventricle myocardium stiffness. When over‐expressing miR‐301a, we found that there is a significant decrease in c‐kit, Dicer, MYH9 and 10. Interestingly, after quantifying miR‐301a expression on these coated plates we found that there is a substantial increase on 15kPa fibronectin‐coated plates. These observations indicate that matrix stiffness may be influencing MSC differentiation via miR‐301a.