Bone marrow mesenchymal stem cell molecular signatures in multiple sclerosis

• Activity Number: 162
• Type: Topic Contributed
• Date/Time: Monday, August 10, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Farren Briggs* and Mark Cameron and Peter Wilkinson and Douglas Gunzler and Sarah Pope Planchon and Jeffrey Cohen
• Companies: Case Western Reserve University and Case Western Reserve University and Case Western Reserve University and Case Western Reserve University and Cleveland Clinic and Cleveland Clinic
• Keywords: Multiple sclerosis ; unsupervised clustering ; multiplatform ; proteomic ; transcriptomic

Abstract

Adult bone marrow mesenchymal stem cells (BM-MSCs) have immunomodulatory and neuroprotective properties, however multiple sclerosis (MS) therapeutic effects of autologous MSC transplantation have been modest. The concern is whether capacity to mitigate damage and promote repair is diminished in MS BM-MSCs. A robust molecular signature of BM-MSCs from MS patients could lead to improved diagnosis and/or prediction of treatment response. This investigation characterizes RNA sequence data (Illumina HiSeq 2500) from BM-MSCs of patients with relapsing-remitting (RR) and secondary-progressive (SP) MS and healthy controls (HC). Differential analyses of the transcriptome compared SPMS cases and HC (4 age/gender matched pairs); and RR and SPMS cases (3 pairs). Pathway activity of top-ranking genes was evaluated using gene set variation analysis. Close analysis of distinguishing expression signatures reveals a reciprocal relationship between type I and type II interferon responses in RR vs SP BM-MCSs, with SP being more type II interferon response aligned (downregulated (PFDR<0.001): IFI6, IFI27, IFI35, IFIT1, IFIT2, and IFIT3; upregulated (PFDR<0.05): IL7 and IL18R1).