VEGF with AMD3100 Endogenously Mobilizes Mesenchymal Stem Cells and Improves Fracture Healing

A significant number of fractures develop non‐union. Mesenchymal stem cell (MSC) therapy may be beneficial, however, this requires cell acquisition, culture and delivery. Endogenous mobilization of stem cells offers a non‐invasive alternative. The hypothesis was administration of VEGF and the CXCR4 antagonist AMD3100 would increase the circulating pool of available MSCs and improve fracture healing. Ex‐breeder female wistar rats received VEGF followed by AMD3100, or sham PBS. Blood prepared for culture and colonies were counted. P3 cells were analyzed by flow cytometry, bi‐differentiation. The effect of mobilization on fracture healing was evaluated with 1.5 mm femoral osteotomy stabilized with an external fixator in 12–14 week old female Wistars. The mobilized group had significantly greater number of cfus/ml compared to controls, p = 0.029. The isolated cells expressed 1.8% CD34, 35% CD45, 61% CD29, 78% CD90, and differentiated into osteoblasts but not into adipocytes. The fracture gap in animals treated with VEGF and AMD3100 showed increased bone volume; 5.22 ± 1.7 µm3 and trabecular thickness 0.05 ± 0.01 µm compared with control animals (4.3 ± 3.1 µm3, 0.04 ± 0.01 µm, respectively). Radiographic scores quantifying fracture healing (RUST) showed that the animals in the mobilization group had a higher healing score compared to controls (9.6 vs. 7.7). Histologically, mobilization resulted in significantly lower group variability in bone formation (p = 0.032) and greater amounts of bone and less fibrous tissue than the control group. Clinical significance: This pre‐clinical study demonstrates a beneficial effect of endogenous MSC mobilization on fracture healing, which may have translation potential to prevent or treat clinical fractures at risk of delayed or non‐union fractures

Postoperative Complications Associated with External Skeletal Fixators in Dogs

OBJECTIVES:  To quantify and evaluate risks of complications attributable to external skeletal fixator (ESF) usage in dogs. METHODS:  A retrospective review of medical records following ESF placement. RESULTS:  Case records of 97 dogs were reviewed; fixator-associated complications occurred in 79/97 dogs. Region of ESF placement was significantly associated with complication development (p = 0.005), not complication type (p = 0.086). Complications developed most frequently in the tarsus (9/10), manus (8/9) and humerus (8/9). Superficial pin-tract infection and implant failure occurred in 38/97 and 17/97 dogs, respectively. Superficial pin-tract infection occurred frequently in the femur, humerus, radius and ulna and the pes, with implant failure frequent in the tarsus and deep pin-tract infection in the manus and tibia. Transarticular frames were significantly more likely to develop a complication (p = 0.028). Age was significantly associated with complication development (p = 0.029). No associations between breed, sex, weight, fracture type (open or closed), ESF classification and the incidence or type of complications were identified. No associations between, breed, age, sex, weight, fracture type (open or closed), ESF classification and the time to complication development were identified. CLINICAL SIGNIFICANCE:  Fixator-associated complications are common in dogs, with the majority of complications related to implant infection. Region and placement of transarticular frames should be carefully considered when selecting stabilization method

Repair of Y-T Humeral Condyle Fractures with Locking Compression Plate Fixation

The aim of this study was to describe the use of locking compression plates (LCP) in Y-T humeral condyle fractures and to evaluate their clinical outcome

CXCR4 Antagonism to Treat Delayed Fracture Healing

A significant number of fractures develop non-union. Stem cell homing is regulated through SDF-1 and its receptor CXCR4. Stem/progenitor cell populations can be endogenously mobilised by administering growth factors with a pharmacological antagonist of CXCR4, AMD3100, which may be a means to improve fracture healing. Methods: A 1.5mm femoral osteotomy in Wistar rats was stabilised with an external fixator. Rats were pre-treated with PBS(P), VEGF(V), IGF-1(I) or GCSF(G) prior to AMD3100. A control group (C) did not receive growth factors or AMD3100. Bone formation after five weeks was analysed. Results: Group P had a significant increase in total bone volume (p=0.01) and group I in % bone in the fracture gap (p=0.035). Group G showed a decrease in bone volume. All treated groups had an increase in trabecular thickness. Histology showed decreased cartilage tissue associated with increased bone in groups with improved healing, and increased fibrous tissue in poorly performing groups. Conclusion: Antagonism of SDF1-CXCR4 axis can boost impaired fracture healing. AMD3100 given alone was the most effective means to boost healing whilst pre-treatment with GCSF reduced healing. AMD3100 is likely mobilizing stem cells into the blood stream that home to the fracture site enhancing healing

Spontaneous dog osteoarthritis — a One Medicine vision

Osteoarthritis (OA) is a global disease that, despite extensive research, has limited treatment options. Pet dogs share both an environment and lifestyle attributes with their owners, and a growing awareness is developing in the public and among researchers that One Medicine, the mutual co-study of animals and humans, could be beneficial for both humans and dogs. To that end, this Review highlights research opportunities afforded by studying dogs with spontaneous OA, with a view to sharing this active area of veterinary research with new audiences. Similarities and differences between dog and human OA are examined, and the proposition is made that suitably aligned studies of spontaneous OA in dogs and humans, in particular hip and knee OA, could highlight new avenues of discovery. Developing cross-species collaborations will provide a wealth of research material and knowledge that is relevant to human OA and that cannot currently be obtained from rodent models or experimentally induced dog models of OA. Ultimately, this Review aims to raise awareness of spontaneous dog OA and to stimulate discussion regarding its exploration under the One Medicine initiative to improve the health and well-being of both species

Epidemiology and clinical management of elbow joint disease in dogs under primary veterinary care in the UK

Conditions affecting the elbow joint are a common cause of lameness in dogs. Primary-care veterinary clinical data are now recognised as a valuable research resource. Using data from the VetCompass Programme, this study aimed to report the frequency and risk factors for elbow joint disease in dogs under primary veterinary care in the UK and describe clinical management

The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats

Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1)