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.

Global miRNA and mRNA expression profiles identify miRNA‐26a‐2‐3p‐dependent repression of IFN signature in systemic sclerosis human monocytes

“…5). Similarly to Di Benedetto et al., our results also demonstrated upregulated expression of miRNA‐10b in SSc [33]. Out of five selected miRNAs, the same expression pattern between miRNA‐seq and qPCR analysis was confirmed only in miRNA‐26a‐2‐3p and miRNA‐485‐3p.…”

Adipose-Derived Stem Cells from Systemic Sclerosis Patients Maintain Pro-Angiogenic and Antifibrotic Paracrine Effects In Vitro

“…Consistent with the presence of antifibrotic factors in SSc-ASC, such as HGF, TIMP-1, and MMP-2, we found that these cells reduced αSMA expression levels and collagen content in DF from SSc patients, demonstrating significant antifibrotic paracrine effects in vitro. These results appear to contrast with recent studies of miRs in silico, which reported a pro-fibrotic ASC signature from SSC patients [23]. Sera from SSc patients have also been shown to favor differentiation of healthy ASC into profibrotic myofibroblast-like cells in vitro [43].…”

“…Although most of these studies have focused on bone-marrow-derived MSC, ASC-based therapies are also controversial. Recent reports of altered molecular signatures in ASC from SSc patients have suggested compromise of their angiogenic and ant-fibrotic activity [23,24,25]; however, few functional studies have been conducted.…”

Endothelial-to-mesenchymal transition in systemic sclerosis

“…New advances for EndMT mediators are represented by miRs. These molecules are small non‐coding RNAs, which are post‐transcriptional repressors of genes [121,122]. Previous studies have shown the involvement of several miRs (miR‐29s, miR‐125b and 126, miR‐130) in the development of EndMT [42] and the interaction between TGF‐β and several miRs (miR‐21, miR‐31, miR‐155) in modulating EndMT [42].…”