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.
Highlights
SSc is a complex multisystem disorder, characterised by microvascular damage, dysregulation of innate and adaptive immunity, and generalized fibrosis in the skin and multiple organs[1,2,3,4,5,6,7,8], such as lungs[9], gastrointestinal tract[10], kidneys[11] and heart[12]
To compare miRs expression patterns among the MSCs derived from different source, we analysed the miRs expression levels by comparing SSc-BM-MSCs with healthy control (HC)-BM-MSCs, and SSc-A-MSCs with HC-A-MSCs as well
Considering the regenerative potential of MSC, displaying immunomodulatory, angiogenic and antifibrotic capabilities, MSC-based therapy could counteract the three main pathogenic axes of SSc17,22,29,30, a clinical setting lacking effective therapy. This is the first paper reporting in silico comparative analysis of miRs profile of MSCs isolated from different sources (BM and A) of SSc patients
Summary
SSc is a complex multisystem disorder, characterised by microvascular damage, dysregulation of innate and adaptive immunity, and generalized fibrosis in the skin and multiple organs[1,2,3,4,5,6,7,8], such as lungs[9], gastrointestinal tract[10], kidneys[11] and heart[12]. In terms of extent, severity, and rate of progression, the optimal therapeutic interventions for SSc is still lacking and, to date, no disease-modifying agents are available[13] and future options include regenerative therapies by using stem cells Among these cells, MSCs are a subset of multipotent cells, which may be identified in a large variety of tissues, including bone marrow, placenta, umbilical cord, adipose tissue, teeth and menstrual fluid, largely involved in the reparative function after damage, suggesting their potential role in regenerative medicine[14,15,16,17,18]. It has been shown that allogenic MSCs infusion is a safe therapy for patients with autoimmune disease, including SSc patients[25] In this developing setting, it is mandatory to better characterise the specific profile of MSCs derived from different sources, to understand if autologous cells may be used in SSc patients, for regenerative medicine. A better knowledge of phenotype and functions of these cells, associated with their stem plasticity, should be considered the first basic step to plan and develop any MSC-based therapy, and to better understand the preliminary results obtained in the small case series of SSc patients treated with MSCs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
