Figure 9.

The effects of the administration of agomir-547-5p or the IL-33 knockdown on BMSC administration-induced analgesia in the CCI model. (a) Effects of the i.v. infusion of vehicle or BMSCs on the MWT (left) and TWL (right) in naive rats. (b) Summary data (mean ± SD) of normalized changes in the MWT or TWL to that right before the application of the vehicle of BMSCs, BMSCs, Agomir-NC, or Agomir-547-5p (= 1, dashed line). V/CCI: vehicle application in the CCI model (see Supplementary Figure 5(f)); BMSCs/CCI: BMSC application in the CCI model (see Supplementary Figure 5(f)); BMSCs/Agomir-547-5p/CCI: BMSCs were applied after the i.t. administration of agomir-547-5p into rats in the CCI model (see Supplementary Figure 5(g)); BMSCs/Agomir-NC/CCI: BMSCs were applied after the i.t. administration of agomir-NC into rats in the CCI model (see Supplementary Figure 5(g)); BMSCs/sh-IL33/CCI: BMSCs were applied after the i.t. infusion of sh-IL-33 into rats in the CCI model (see Supplementary Figure 5(h)). BMSCs/sh-NC/CCI: BMSCs were applied after the i.t. infusion of sh-NC into rats in the CCI model (see Supplementary Figure 5(h)). Agomir-547-5p/BMSCs/CCI: Agomir-547-5p was applied after the i.v. administration of BMSCs into rats in the CCI model (see Supplementary Figure 5(i)); ***p < 0.001 (unpaired t test in comparison with that of the BMSC application after vehicle, agomir-NC, or sh-NC infusion in the CCI model). Values in brackets indicate the number of rats tested. (c) A diagram shows that via depressing miRNA-547-5p the CCI induces the IL-33/ST2 signaling upregulation and pain hypersensitivity and that via blocking the miRNA-547-5p-mediated IL-33/ST2 signaling, BMSCs reduce the CCI-induced pain hypersensitivity.

BMSC: bone marrow stromal cell; MWT: mechanical withdrawal threshold; TWL: thermal withdrawal latency; IL33: interleukin-33; NC: nonspecific negative control sequence; CCI: constriction nerve injury; ST2: suppressor of tumorigenicity 2; miRNA: microRNA.