Comparative efficacy of dermal fibroblast-mediated and direct adenoviral bone morphogenetic protein-2 gene therapy for bone regeneration in an equine rib model.

Cell-mediated and direct adenoviral (Ad) vector gene therapies can induce bone regeneration, including dermal fibroblasts (DFbs). We compared two effective therapies, DFb-mediated and direct Ad vector delivery of bone morphogenetic protein-2 (BMP2), for relative efficacy in bone regeneration. Equine rib drill defects were treated by percutaneous injection of either DFb-BMP2 or an Ad-BMP2 vector. At week 6, both DFb-BMP2- and Ad-BMP2-treated rib defects had greater bone filling volume and mineral density, with DFb-BMP2 inducing greater bone volume and maturity in the cortical bone aspect of the defect than Ad-BMP2. The transplantation of DFb alone induced modest bone formation. Increased mineral density and bone turnover were evident in the cortical and cancellous bone directly adjacent to the healing drill defects treated with either DFb-BMP2 or Ad-BMP2. Using our cell/vector dosage and model, BMP2, whether delivered by the DFb vector or direct Ad vector, induced greater and robust bone regeneration. DFb-mediated BMP2 therapy promoted greater cortical bone regeneration than did direct gene delivery, possibly because of an increased cellularity of the bone healing site. BMP2 delivery, regardless of gene delivery method, increased the mineral density of the neighboring bone, which may be beneficial clinically in repairing or weak bone.

Ablation of the nephrosplenic space for treatment of recurring left dorsal displacement of the large colon in a racehorse.

Left dorsal displacement of the large colon was diagnosed in a 3-year-old Thoroughbred gelding. Conservative treatment that included lunging after administration of phenylephrine and rolling while under general anesthesia was not successful. The displaced segment of colon was reduced surgically through a ventral midline incision, but displacement recurred 4 days after surgery. Ablation of the nephrosplenic space by suturing the nephrosplenic ligament to the splenic capsule was performed through the left flank. At followup 1 year after surgery, the horse had not had further signs of colic and had returned to racing. Other methods to prevent large colon displacement, including colon resection and colopexy, are not recommended for athletic horses. Ablation of the nephrosplenic space, however, may be efficacious.