Identification of Potential Plasma microRNA Stratification Biomarkers for Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells in Rheumatoid Arthritis

Author:

Mallinson David J.1,Dunbar Donald R.1,Ridha Susan1,Sutton Elizabeth R.1,De la Rosa Olga2,Dalemans Wilfried3,Lombardo Eleuterio2

Affiliation:

1. a Sistemic Ltd., West of Scotland Science Park, Kelvin Campus, Glasgow G20 0SP, United Kingdom

2. b TiGenix SAU, Calle Marconi, Parque Tecnológico de Madrid, Tres Cantos 28760, Madrid, Spain

3. c TiGenix NV, RomeinseStraat 12/2 3001, Leuven, Belgium

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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