Medial patellar luxation induces cartilage erosion in dogs: a retrospective study of prevalence and risk factors.

OBJECTIVE: To explain the relationship between cartilage erosion and medial patellar luxation (MPL) and to identify risk factors in dogs. METHODS: A retrospective review was conducted on 90 dogs (103 stifles) surgically treated for MPL between January 2006 and March 2024. Data collected included signalment, side of operated stifle, patellar luxation grade, symptom duration, and lameness score. Cartilage erosion was evaluated for extent and location on the patella and femoral trochlea. Statistical analyses were conducted to identify risk factors. RESULTS: The prevalence of cartilage erosion of the patella and femoral trochlea was 47.6% (49/103) and 54.4% (56/103), respectively, increasing with a higher grade of patellar luxation. Lesions were most prevalent in the distolateral patella and proximomedial trochlea, with generalized lesions more prevalent in grade IV. The extent of both lesions was significantly associated with age, patellar luxation grade, and symptom duration, while body weight significantly correlated only with the cartilage erosion of the patella. No significant correlation was observed with sex, side of operated stifle, or lameness score. CONCLUSIONS: Many patients with MPL exhibited cartilage erosion in the patellofemoral joint, likely due to biomechanical mechanisms. Surgery can be indicated for patients with MPL, as it may prevent cartilage erosion while improving patellofemoral alignment and gait. When selecting surgical candidates, it is important to consider risk factors, such as patellar luxation grade, body weight, age, and symptom duration. CLINICAL RELEVANCE: Early surgical treatment is recommended, especially for dogs with higher body weight and higher grade of MPL, to prevent cartilage erosion and secondary osteoarthritis.

Cervical spine reconstruction after total vertebrectomy using customized three-dimensional-printed implants in dogs.

BACKGROUND: Sufficient surgical resection is necessary for effective tumor control, but is usually limited for vertebral tumors, especially in the cervical spine in small animal neurosurgery. OBJECTIVE: To evaluate the primary stability and safety of customized three-dimensional (3D)-printed implants for cervical spine reconstruction after total vertebrectomy. METHODS: Customized guides and implants were designed based on computed tomography (CT) imaging of five beagle cadavers and were 3D-printed. They were used to reconstruct C5 after total vertebrectomy. Postoperative CT images were obtained to evaluate the safety and accuracy of screw positioning. After harvesting 10 vertebral specimens (C3-C7) from intact (group A) and implanted spines (group B), implant stability was analyzed using a 4-point bending test comparing with groups A and C (reconstituted with plate and pins/polymethylmethacrylate after testing in Group A). RESULTS: All customized implants were applied without gross neurovascular damage. In addition, 90% of the screws were in a safe area, with 7.5% in grade 1 (< 1.3 mm) and 2.5% in grade 2 (> 1.3 mm). The mean entry point and angular deviations were 0.81 ± 0.43 mm and 6.50 ± 5.11°, respectively. Groups B and C significantly decreased the range of motion (ROM) in C3-C7 compared with intact spines (p = 0.033, and 0.018). Both groups reduced overall ROM and neutral zone in C4-C6, but only group B showed significance (p = 0.005, and 0.027). CONCLUSION: Customized 3D-printed implants could safely and accurately replace a cervical vertebra in dog cadavers while providing primary stability.

Transplantation of Heat-Shock Preconditioned Neural Stem/Progenitor Cells Combined with RGD-Functionalised Hydrogel Promotes Spinal Cord Functional Recovery in a Rat Hemi-Transection Model.

BACKGROUND: Neural stem/progenitor cell (NSPC) transplantation in spinal cord injury (SCI) is a potential treatment that supports regeneration by promoting neuroprotection, remyelination, and neurite outgrowth. However, glial scarring hinders neuroregeneration and reduces the efficiency of cell transplantation. The present study aimed to enhance this neuroregeneration by surgically removing the glial scar and transplanting heat-shock (HS) preconditioned NSPCs in combination with Arg-Gly-Asp (RGD)-functionalised hydrogel in a rat spinal cord hemi-transection model. METHODS: Twelve Sprague-Dawley rats underwent spinal cord hemi-transection and were randomly divided into three treatment groups: hydrogel implantation (control group), NSPC-encapsulated hydrogel implantation, and HS-NSPC-encapsulated hydrogel implantation. HS preconditioning was applied to the NSPCs to reinforce cell retention and an RGD-functionalised hydrogel was used as a biomatrix. RESULTS: In vitro culture showed that preconditioned NSPCs highly differentiated into neurons and oligodendrocytes and exhibited higher proliferation and neurite outgrowth in hydrogels. Rats in the HS-NSPC-encapsulated hydrogel implantation group showed significantly improved functional recovery, neuronal and oligodendrocyte differentiation of transplanted cells, remyelination, and low fibrotic scar formation. CONCLUSIONS: The surgical removal of the glial scar in combination with HS-preconditioning and RGD-functionalised hydrogels should be considered as a new paradigm in NSPC transplantation for spinal cord regeneration treatment.

Three-dimensional-printed patient-specific guides for tibial deformity correction in small-breed dogs.

OBJECTIVE: To describe the use of patient-specific 3-D-printed osteotomy, reduction, and compression guides for tibial closing wedge osteotomy in small-breed dogs. ANIMALS: 6 dogs with unilateral tibial deformities. METHODS: Six small-breed dogs with 1 or a combination of tibial deformities, including excessive tibial plateau angle, valgus, and torsion, were scheduled to undergo tibial closing wedge osteotomy using patient-specific 3-D-printed osteotomy, reduction, and compression guides. The location and orientation of the wedge osteotomy were determined based on CT data using computer-aided design software. After the tibial deformities were corrected, postoperative CT or radiographs were obtained to compare the achieved tibial limb angles with the planned angles. Clinical evaluation and radiographic follow-up were performed on all dogs. RESULTS: Guides were successfully positioned at each specific location, and osteotomies were performed without radiation exposure or observer assistance in all dogs. Tibial deformities were corrected with angular errors of 1.8 ± 1.4°, 2.3 ± 2.1°, and 2.6 ± 1.3° in the sagittal, frontal, and transverse planes, respectively. Mild complications resolved within 1 month in 3 dogs, and revision surgery was not required. Five dogs improved to the normal gait (mean, 14.8 ± 6.6 weeks), and 1 dog recovered a satisfactory gait 24 weeks after surgery. All limbs healed 14 ± 4.7 weeks after surgery. CLINICAL RELEVANCE: Patient-specific 3-D-printed osteotomy, reduction, and compression guides can provide effective assistance allowing accurate correction of tibial deformities. Their use yields good clinical outcomes in small-breed dogs.

Heat-Shock Proteins Can Potentiate the Therapeutic Ability of Cryopreserved Mesenchymal Stem Cells for the Treatment of Acute Spinal Cord Injury in Dogs.

BACKGROUND: Mesenchymal stem cells (MSCs) are applied in the treatment of spinal cord injury (SCI) because of their neural tissue restoring ability. In the clinical setting, intravenous injection of cryopreserved cells is essential for the immediate treatment of SCI, exhibiting the disadvantage of reduced cell properties. METHODS: In this study, we potentiated the characteristics of cryopreserved MSCs by heat-shock (HS) treatment to induce the expression of HS protein (HSP) HSP70/HSP27 and further improved antioxidant capacity by overexpressing HSP32 (heme oxygenase-1 [HO-1]). We randomly assigned 12 beagle dogs with acute SCI into three groups and transplanted cells intravenously: (i) F-MSCs (MSCs in frozen/thawed conditions); (ii) F-HSP-MSCs (HS-treated MSCs in frozen/thawed conditions); and (iii) F-HSP-HO-MSCs (HO-1-overexpressing and HS-treated MSCs in frozen/thawed conditions). RESULTS: The potentiated MSCs exhibited increased growth factor-, anti-inflammatory-, antioxidant-, homing- and stemness-related gene expression. In the animal experiments, the HSP-induced groups showed significant improvement in hind-limb locomotion, highly expressed neural markers, less intervened fibrotic changes, and improved myelination. In particular, the HO-1-overexpression group was more prominent, controlling the initial inflammatory response with high antioxidant capabilities, suggesting that antioxidation was important to prevent secondary injury. Accordingly, HSPs not only successfully increased the ability of frozen MSCs but also demonstrated excellent neural protection and regeneration capacity in the case of acute SCI. CONCLUSIONS: The application of HSP-induced cryopreserved MSCs in first-aid treatment for acute SCI is considered to help early neural sparing and further hind-limb motor function restoration.

Intravenous Administration of Heat Shock-Treated MSCs Can Improve Neuroprotection and Neuroregeneration in Canine Spinal Cord Injury Model.

Transplantation of mesenchymal stem cells (MSCs) is a promising treatment for spinal cord injury (SCI). However, many transplanted cells die within a few days, eventually limiting the efficacy of cellular therapy. To overcome this problem, we focused on the potential of heat shock (HS) proteins in facilitating recovery from cell damage and protecting against cytotoxicity. PCR results showed that the expression of neurotrophic factor, anti-inflammatory, stemness, and homing genes increased in HS-treated MSCs. We investigated whether HS-treated MSCs could promote recovery of hindlimb function in an acute canine SCI model. We compared the effects of intravenous transplantation with (i) lactated Ringer's solution as a control, (ii) green fluorescent protein-expressing MSCs (MSCs-GFP), and (iii) GFP-expressing and HS-treated MSCs (MSCs-GFP-HS). Spinal cords were harvested at four weeks and used for Western blot and histopathological analyses. The MSCs-GFP-HS group showed significant improvements in hindlimb function from weeks 3 and 4 compared with the other groups. This group also showed higher expression of neural markers, fewer intervening fibrotic changes, and pronounced myelination. These results suggest that induction of an HS response in MSCs could promote neural sparing. In conclusion, transplantation of HS-treated MSCs could improve neuroprotection and neuroregeneration in acute SCI.

Therapeutic effects of platelet derived growth factor overexpressed-mesenchymal stromal cells and sheets in canine skin wound healing model.

Adipose-derived mesenchymal stromal cells (Ad-MSCs) have excellent potential for skin wound repair. Moreover, platelet-derived growth factor (PDGF) has strong wound healing properties. The purpose of the present study was to compare the healing effects of PDGF-overexpressing canine allogeneic Ad-MSCs (PDGF-MSCs) and their cell sheets (PDGF-CSs) as compared to unexpressed Ad-MSCs (U-MSCs) and their cell sheets (UCSs) in a cutaneous wound healing model induced upon dogs. In in vitro study, the expression of immunomodulatory and growth factors was assessed by qRT-PCR. In in vivo study, cells and sheets were transplanted into a square-shaped full-thickness (1.5×1.5 cm) skin defect model created in 12 dogs. After 5 and 10 days, wounds were harvested and evaluated macroscopically and histopathologically. The qRT-PCR results showed that the PDGF-B gene was significantly upregulated (p<0.05) in PDGF-CS and PDGF-MSCs groups. Upon gross analysis of the wound, all stromal cells and their sheet groups showed accelerated (p<0.05) cutaneous wound healing compared to the negative control groups. As compared to U-MSCs and UCSs, the PDGF-MSCs showed significant epithelization on days 5 and 10 of healing, whereas PDGF-CSs showed improved epithelization only on day 10. In the granulation tissue analysis, PDGF-CSs and UCSs promoted more formation (p<0.05) of upper granulation tissue, collagen, and activated fibroblasts than PDGF-MSCs, and U-MSCs. Especially, the PDGF-CSs presented the highest formation and maturation of granulation tissue among all groups. All considered, PDGF overexpressed stromal cells or cells sheets can improve cutaneous wound healing in a canine model.