Background
Due to their self-renewal capacity, multi-lineage potential, and immunomodulatory properties, mesenchymal stromal cells (MSCs) are an attractive tool for different therapeutic strategies. Foreskin (FSK), considered as a biological waste material, has already been shown to be a valuable source of MSCs. Besides their typical fibroblast like morphology and International Society for cellular Therapy compliant phenotype, foreskin-MSCs (FSK-MSCs) are clonogenic, and highly proliferative cells with multi-lineage and strong immunomodulatory capacities. Of importance, FSK-MSCs properly adjust their fate following exposure to inflammatory signals. Being potent regulators of gene expression, miRNAs are involved in modulating nearly all cellular processes and in orchestrating the roles of different immune cells. In this study, we characterized the miRNome of FSK-MSCs by determining the expression profile of 380 different miRNAs in inflammation primed vs. control non-primed cells.
Conclusions
After determining their miRNome, we identified a striking effect of inflammatory signals on the miRNAs' expression levels in FSK-MSCs. Our results highlight a potential role of miRNAs in modulating the transcription programs of FSK-MSCs in response to inflammatory signals. Further, we propose that specific miRNAs could serve as interesting targets to manipulate some functions of FSK-MSCs, thus ameliorating their therapeutic potential.
Methods
TaqMan low density array (TLDA) was performed to identify dysregulated miRNAs after exposing FSK-MSCs to inflammatory signals. Quantitative real-time RT-PCR was carried out to validate the observations. DIANA-miRPath analysis web server was used to identify potential pathways that could be targeted by the dysregulated miRNAs.
Results
Sixteen miRNAs were differentially expressed in inflammation-primed vs. non-primed FSK-MSCs. The expression level of miR-27a, -145, -149, -194, -199a, -221, -328, -345, -423-5p, -485-3p, -485-5p, -615-5p and -758 was downregulated whilst that of miR-155, -363 and -886-3p was upregulated. Target pathway prediction of those differentially expressed miRNAs identified different inflammation linked pathways. Conclusions: After determining their miRNome, we identified a striking effect of inflammatory signals on the miRNAs' expression levels in FSK-MSCs. Our results highlight a potential role of miRNAs in modulating the transcription programs of FSK-MSCs in response to inflammatory signals. Further, we propose that specific miRNAs could serve as interesting targets to manipulate some functions of FSK-MSCs, thus ameliorating their therapeutic potential.