Natural conditioning of mesenchymal stem cells from multiple sclerosis patients enhances their immune-modulating potential

Abstract

Background & Aim Background Multiple sclerosis (MS) is the most frequent chronic inflammatory, demyelinating and neurodegenerative disease of the Central Nervous System (CNS) in young adults. The use of Autologous Mesenchymal stem cells (MSCs) have been investigated to treat MS for the past decades .Outcomes of non-standardized clinical trials have been inconsistent and calls for the use of allogenic MSCs have recently increased due to suggestions that the disease is affecting the therapeutic aspects of MSCs. Aim This work aims to investigate the influence of the genetic makeup of MS patients, the environmental factors involved in the etiology of MS or the immunomodulatory drugs taken by patients on their Bone Marrow derived Mesenchymal Stem Cells (MS-MSCs) compared to healthy donors, Control MSCs (CTR-MSCs). MSCs characteristics and immune- modulatory therapeutic potential was analyzed. Methods, Results & Conclusion Methods MSCs from 8 MS patients and 3 controls were characterized using microscopy, flow cytometry of surface markers, tri-lineage inherent and induced differentiation potential. For a comprehensive analysis on the transcriptome level, Affymetrix HTA microarray chips were used. In addition, Multiplex Enzyme Linked Immunosorbent Assay (ELISA) immunoassay to assess the Cytokine and chemokine secretion by MSCs was performed using the 27-plex human inflammatory kit (Biorad). Furthermore, coculture experiments of MS-MSCs from with T cells and DCs were conducted. Results MS-MSCs passed all the MScs characterization criteria. Microarray Analysis reveals the differential expression of two disease associated markers in MS-MSCs; miRNA-599 and the signal transducing gene T-cell activation RhoGTPase activating protein TAGAP. On the other hand, MS-MSCs showed an upregulation of important immunoregulatory genes in MS-MSCs such as TGFb1, the potent Treg differentiation factor. Moreover, IL-10 and other anti-inflammatory cytokines’ levels were higher in co-cultures of T cells with MS-MSCs. While, mDCs decreased in co-cultures with MS-MSCs. Conclusion The MS disease-related or medication-related cellular and biochemical changes in the bone marrow microenvironment does not appear to have a negative impact on the immune- modulation potential of BM-MSCs. On the contrary, there seem to have a positive conditioning effect of the inflammatory milieu which enhances the modulation of both the innate and the adaptive immunity.