Comparative miRNA-Based Fingerprinting Reveals Biological Differences in Human Olfactory Mucosa- and Bone-Marrow-Derived Mesenchymal Stromal Cells.
Previously we reported that nestin-positive human mesenchymal stromal cells (MSCs) derived from the olfactory mucosa (OM) enhanced CNS myelination in vitro to a greater extent than bone-marrow-derived MSCs (BM-MSCs). miRNA-based fingerprinting revealed the two MSCs were 64% homologous, with 26 miRNAs differentially expressed. We focused on miR-146a-5p and miR-140-5p due to their reported role in the regulation of chemokine production and myelination. The lower expression of miR-140-5p in OM-MSCs correlated with higher secretion of CXCL12 compared with BM-MSCs. Addition of CXCL12 and its pharmacological inhibitors to neural co-cultures supported these data. Studies on related miR-146a-5p targets demonstrated that OM-MSCs had lower levels of Toll-like receptors and secreted less pro-inflammatory cytokines, IL-6, IL-8, and CCL2. OM-MSCs polarized microglia to an anti-inflammatory phenotype, illustrating potential differences in their inflammatory response. Nestin-positive OM-MSCs could therefore offer a cell transplantation alternative for CNS repair, should these biological behaviors be translated in vivo.
Institute of Infection, Inflammation and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Susan Louise
SL
Lindsay
Institute of Infection, Inflammation and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Steven Andrew
SA
Johnstone
Institute of Infection, Inflammation and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Michael Anthony
MA
McGrath
Institute of Infection, Inflammation and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK; Sistemic UK, Kelvin Campus, Maryhill Road, Glasgow G20 0SP, UK.
David
D
Mallinson
Institute of Infection, Inflammation and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK. Electronic address: susan.barnett@glasgow.ac.uk.
Susan Carol
SC
Barnett
D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D054377:Chemokine CXCL12 / Q000235:genetics; D016172:DNA Fingerprinting; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics
D054377:Chemokine CXCL12; D035683:MicroRNAs; D051193:Toll-Like Receptors