Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts

Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, due to an immune reaction against myelin proteins. Multipotent mesenchymal stromal cells (MSCs) present immunosuppressive effects and have been used for the treatment of autoimmune diseases. In our study, gene expression profile and in vitro immunomodulatory function tests were used to compare bone marrow-derived MSCs obtained from MS patients, at pre-and postautologous hematopoietic stem cell transplantation (AHSCT) with those from healthy donors. Patient MSCs comparatively exhibited i) senescence in culture; ii) similar osteogenic and adipogenic differentiation potential; iii) decreased expression of CD105, CD73, CD44, and HLA-A/B/C molecules; iv) distinct transcription at pre-AHSCT compared with control MSCs, yielding 618 differentially expressed genes, including the downregulation of TGFB1 and HGF genes and modulation of the FGF and HGF signaling pathways; v) reduced antiproliferative effects when pre-AHSCT MSCs were cocultured with allogeneic T-lymphocytes; vi) decreased secretion of IL-10 and TGF-b in supernatants of both cocultures (pre-and post-AHSCT MSCs); and vii) similar percentages of regulatory cells recovered after MSC cocultures. The transcriptional profile of patient MSCs isolated 6 months posttransplantation was closer to pre-AHSCT samples than from healthy MSCs. Considering that patient MSCs exhibited phenotypic changes, distinct transcriptional profile and functional defects implicated in MSC immunomodulatory and immunosuppressive activity, we suggest that further MS clinical studies should be conducted using allogeneic bone marrow MSCs derived from healthy donors. We also demonstrated that treatment of MS patients with AHSCT does not reverse the transcriptional and functional alterations observed in patient MSCs.

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

“…Disease association is another application of comparative transcriptome analysis to MSC populations derived from control and pathological states (Benisch et al, 2012;Binato et al, 2015;de Oliveira et al, 2015;Huang, J.C. et al, 2015;Li et al, 2012). Remarkable abnormality in gene expression was observed in human BM-MSCs from aplastic anaemia patients when compared with those from healthy volunteers (Li et al, 2012).…”

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

“…Given MSCs putative roles in immunosuppression and neural repair, they have also recently been proposed as treatment for MS. In addition, the results showed that patient MSCs exhibited phenotypic changes, distinct transcriptional profile and functional defects implicated in MSC immunomodulatory and immunosuppressive activity [164]. [167].…”

Influence of the intensity and loading time of direct current electric field on the directional migration of rat bone marrow mesenchymal stem cells

“…ALP is an early marker of osteogenic differentiation which can be hydrolyzed to release inorganic phosphate. The expression level of ALP increased to a certain extent, reflecting the ability of the cells to enhance osteogenesis [26]. RUNX2 is essential for osteoblastic differentiation and the bone formation and maintenance [27].…”