title: Identification of Potential Plasma microRNA Stratification Biomarkers for Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells in Rheumatoid Arthritis.
abstract: The ability to identify and stratify patients that will respond to specific therapies has been transformational in a number of disease areas, particularly oncology. It is anticipated that this will also be the case for cell-based therapies, particularly in complex and heterogeneous diseases such as rheumatoid arthritis (RA). Recently, clinical results with expanded allogenic adipose-derived mesenchymal stem cells (eASCs) have indicated clinical efficacy in highly refractory RA patients. In this study, we set out to determine if circulating microRNAs (miRNAs) could be identified as potential biomarkers associated with response to eASCs in these RA patients. The miRNA expression profiles of pre-treatment plasma samples from responder and nonresponder patients were determined using microarrays. Ten miRNAs were identified that were differentially expressed in the responder group as compared to the nonresponder group. To confirm the differential expression of these 10 miRNA biomarkers, they were further assayed by quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR). From this analysis, three miRNAs, miR-26b-5p, miR-487b-3p and miR-495-3p, were confirmed as being statistically significantly upregulated in the responder group as compared with the nonresponder group. Receiver operating characteristic analysis confirmed their diagnostic potential. These miRNAs could represent novel candidate stratification biomarkers associated with RA patient response to eASCs and are worthy of further clinical validation. Stem Cells Translational Medicine 2017;6:1202-1206.
authors.affiliation: Sistemic Ltd., West of Scotland Science Park, Kelvin Campus, Glasgow, G20 0SP, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mallinson
authors.affiliation: Sistemic Ltd., West of Scotland Science Park, Kelvin Campus, Glasgow, G20 0SP, United Kingdom.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Dunbar
authors.affiliation: Sistemic Ltd., West of Scotland Science Park, Kelvin Campus, Glasgow, G20 0SP, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Ridha
authors.affiliation: Sistemic Ltd., West of Scotland Science Park, Kelvin Campus, Glasgow, G20 0SP, United Kingdom.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sutton
authors.affiliation: TiGenix SAU, Calle Marconi, Parque Tecnológico de Madrid, Tres Cantos, 28760, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: De la Rosa
authors.affiliation: TiGenix NV, RomeinseStraat 12/2, 3001, Leuven, Belgium.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dalemans
authors.affiliation: TiGenix SAU, Calle Marconi, Parque Tecnológico de Madrid, Tres Cantos, 28760, Madrid, Spain.
authors.forename: Eleuterio
authors.initials: E
authors.lastname: Lombardo
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000628:therapy*; D015415:Biomarkers / Q000097:blood*; D064987:Cell- and Tissue-Based Therapy; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D035683:MicroRNAs / Q000097:blood*; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Adipose mesenchymal stem cells; Cell-based therapy; MicroRNA; Plasma stratification biomarkers; Rheumatoid arthritis