Mesenchymal stem cells of Systemic Sclerosis patients, derived from different sources, show a profibrotic microRNA profiling

Abstract

Systemic Sclerosis (SSc) is a disease with limited therapeutic possibilities. Mesenchymal stem cells (MSCs)-therapy could be a promising therapeutic option, however the ideal MSCs source has not yet been found. To address this problem, we perform comparison between bone marrow (BM)-MSCs and adipose (A)-MSCs, by the miRs expression profile, to identify the gene modulation in these two MSCs source. MicroRNAs (miRs) are RNAs sequences, regulating gene expression and MSCs, derived from different tissues, may differently respond to the SSc microenvironment. The miRs array was used for the miRs profiling and by DIANA-mirPath tool we identified the biological functions of the dysregulated miRs. In SSc-BM-MSCs, 6 miRs were significantly down-regulated and 4 miRs up-regulated. In SSc-A-MSCs, 11 miRs were significantly down-regulated and 3 miRs up-regulated. Interestingly, in both the sources, the involved pathways included the senescence mechanisms and the pro-fibrotic behaviour. Furthermore, both the MSCs sources showed potential compensatory ability. A deeper knowledge of this miRs signature might give more information about some pathogenic steps of the disease and in the same time clarify the possible therapeutic role of autologous MSCs in the regenerative therapy in SSc.

Figure 1

MiRs volcano plots. MiRs volcano plots of SSc-BM-MSC (A,B) and SSc-A-SSC (C,D). MicroRNAs’ distribution, obtained from TaqMan array human microRNA set A (in A,C) and set B (in B,D) was reported. In green are reported all the miRs down regulated, in red all the miRs up-regulated. Analyses were performed by using Expression Suite software. Y axis: p value (−log10), p = 0,05 threshold in blue. X axis: fold change (log2), black vertical lines indicate 0,5 (left) and 2 (right) fold change.

Figure 2

Venn diagram. Venn diagram shows the numbers of miRs expressed in Profile BM (blue) and the numbers of miRs expressed in Profile A (red). The Profile BM and Profile A do not share any miRs expression.

Figure 3

Graphical visualization of miRNA-target interactions. Neo4J software graphical visualization of miRNA-target interactions, concerning the Profile BM (left) and Profile (right) A. Red circles represent miRNAs. Blue circles represent genes that interact with the miRs, experimentally supported in TarBase. Purple circles represent the relevant pathways, that include validated target genes. Both the Profile BM and Profile A share “TGF-beta Signalling Pathway” and “Signaling Pathways Regulating Pluripotency Of Stem Cells”.