Abstract 14310: Microrna-155 Inhibits Cell Migration in Human Cardiomyocyte Progenitor Cells Mediated by Mmp2 and Mmp9
Stem cell therapy to regenerate the injured heart is promising, but many issues remain to be addressed. In the last years small RNA molecules, i.e. microRNAs (miRNAs), have been found to keep tight control of cell specifications and cardiac functions by gene or gene cluster silencing. One of these miRNAs, miRNA-155 (miR-155), a typical multifunctional miRNA, has been put forward. Increased evidence indicates that miR-155 is involved in numerous biological processes, including cell differentiation ,survival, and immune responses. In a microarray profile of human-derived cardiomyocyte progenitor cells (CMPCs), miR-155 was highly present. Combined with the initiative to improve cardiac regeneration with cell therapy, miR-155 emerges as an interesting target. Here, we investigated the potential role of miR-155 on cell migration in human CMPCs and the possible underlying mechanism.
Methods and results: Human CMPCs were isolated, cultured and expanded in vitro. Cells were transfected with miR-155, miR-155 antimiR or scramble-miR. At 24 hours post transfection, a scratch wound assay was performed. MiR-155 overexpression efficiently inhibited cell migration by 24±3.1% as compared to control. In concurrence, in a transwell assay, miR-155 transfected cells showed a reduction in migration of 27±4.5%. Furthermore, gelatinase zymography was performed on conditioned medium from miR-155 transfected CMPCs and showed a significant decrease in MMP2 and MMP9 activities. MMP-2 and 9 are not predicted as direct targets of miR-155, thus mechanistic studies are ongoing.
Conclusion: MiR-155 inhibits cell migration in human CMPCs, possibly mediated by decreased MMP2 and MMP9 activities, providing an opportunity to achieve better cell retention upon imaging guided cell delivery.
- © 2010 by American Heart Association, Inc.