期刊
STEM CELL REPORTS
卷 6, 期 5, 页码 729-742出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2016.03.009
关键词
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资金
- Tenovus Foundation
- Medical Research Council (MRC) [MR/J004731/1]
- Lord Kelvin/Adam Smith University of Glasgow
- NC3Rs [NC/K50032X/1]
- MRC [MR/J004731/1] Funding Source: UKRI
- Medical Research Council [MR/J004731/1] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/K50032X/1] Funding Source: researchfish
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.
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