XXXX by baculovirus-engineered bone marrow-derived MSCs expressing MicroRNA sponges.

@entity3604 @entity71172 @entity71173 @entity170 @entity79 @entity2095 @entity35
UNASSIGNED: Fractures associated with @entity170 are a worldwide health problem. To augment @entity3604 bone healing, we aimed to develop a cell/gene therapy approach in combination with miRNA manipulation. We unraveled aberrant overexpression of @entity71172 * and @entity71173 in the bone marrow-derived MSCs isolated from ovariectomized (OVX) @entity35 (OVX-BMSCs). To suppress the miRNA levels, we constructed hybrid baculovirus vectors expressing miRNA sponges to antagonize @entity71172 * or @entity71173 . Engineering OVX-BMSCs with the hybrid vectors persistently attenuated the cellular @entity71172 */ @entity71173 levels, which promoted the OVX-BMSCs osteogenesis and augmented the ability of OVX-BMSCs to repress osteoclast maturation in  vitro. Notably, suppressing @entity71173 exerted more potent osteoinductive effects. In the @entity3604 @entity35 models with a critical-size bone defect at the femoral metaphysis, implanting the OVX-BMSCs ectopically expressing @entity2095 failed to heal the defect, which underscored the difficulty to heal @entity79 . Nonetheless, allotransplantation of the @entity71173 sponges-expressing OVX-BMSCs healed the defect and ameliorated the bone quality (density, trabecular number, trabecular thickness and trabecular space) at 4 weeks post-implantation. Co-expressing @entity2095 and @entity71173 sponges in OVX-BMSCs further synergistically substantiated the healing. The baculovirus-engineered OVX-BMSCs that expressed @entity71173 sponge, with or without @entity2095 expression, thus paved a new avenue to the treatment of @entity79 .
