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force plate gait analysis associated with osteoarthritis observed mostly in the hip joint [22,25,26,114,115], elbow [116], and humeroradial joint [117] (Table 5). https://vetsci.org https://doi.org/10.4142/jvs.2020.21.e42 9/22 Stem-cell therapy in dogs and cats In tendon injuries, autologous BMSCs combination with custom orthosis have great potential for modulating inflammation and stimulating tendon regeneration [118]. After autologous MSCs transplantation, lameness resolved and peak vertical and propulsive forces of contralateral pelvic limb increased. However, incomplete healing was observed via serial orthopedic and ultrasound examinations, so further research is required for clinical application of stem cells in tendon injuries. Hip dysplasia (HD) is an inherited orthopedic disease that affects dogs of all breeds. Common treatments applied in HD dogs include an energy-restricted diet, exerciserestriction, medical management with analgesics and/or chondroprotective agents, or surgical correction [119]. One study used autologous or allogeneic adipose-derived stem cells in 9 HD dogs [24]. Acupoint was suggested as a stem cell injection site, and stem cell administration resulted in functional improvement and marked decrease in pain on manipulation in 8 dogs with HD. Only one dog showed no remarkable improvements or pathological alterations. https://vetsci.org https://doi.org/10.4142/jvs.2020.21.e42 10/22 Stem-cell therapy in dogs and cats Table 5. Veterinary clinical stem cell trials in musculoskeletal disease Disease Cell therapy No. of dogs Control Evaluation periods/effects Ref. OA (hip joint) Autologous AD-MSCs; intraarticular injection; 4.2–5 × 106 cells 18 dogs divided to stem cell and control group (injection of placebo material) Yes At 30, 60, and 90 days; the results showed significantly improved scores for lameness and the compiled scores for lameness, pain, and range of motion. [22] OA (hip joint) Autologous AD-MSCs; intraarticular injection; 30 × 106 cells 9 dogs in stem cell group; 5 healthy dogs in control group Yes At 30, 90, 180 days; improvement of limb function in dogs with hip OA was objectively seen. [25] OA (hip joint) Autologous AD-MSCs; intraarticular injection; 30 × 106 cells 8 dogs in stem cell group; 5 healthy dogs in control group Yes At 30, 90, 180 days; reduced lameness due to OA was observed after stem cell therapy. [26] OA (hip joint) Autologous AD-MSCs; intraarticular injection; 30 × 106 cells 18 dogs in stem cell group; 17 dogs in PRGF group Yes At 1, 3, 6 months; Both groups showed safe and effective outcome and compared to PRGF, cell group showed better results at 6 months. [114] OA (hip joint) Autologous AD-MSCs; intraarticular injection; 30 × 106 cells 10 dogs in stem cell group; 5 healthy dogs in control group Yes At 30, 90, 180 days; MSC therapy significantly improved limb function in dogs with hip OA. [115] OA (elbow joint) Autologous AD-MSCs; intraarticular injection; 3-5 × 106 cells 14 dogs in stem cell group No At 30, 60, 90, and 180 days; statistically significant improvement in lameness, range of motion, and pain on manipulation over time was shown. [116] OA (humeroradial joint) Autologous AD-MSCs; intraarticular injection; 3–5 × 106 cells 4 dogs in stem cell group No At 1 week and 1 month; cellular therapy has a significant potential for clinical use inducing functional improvements. [117] Skeletal muscle injury Autologous AD stem cells; case 1, intralesional and IV; 4.7 × 106 cells each, case 2, intralesional 7.5 × 106 cells and IV 3.8 × 106 cells 2 dogs No At 19 weeks (case 1) and 22 weeks (case 2); significant reduction in lesion size and clinical improvements [111] Semitendinosus myopathy Autologous AD-MSCs; intralesional and IV 11 dogs in stem cell group No At 6 months and 1 year; stem cell treatment helped prevent progression, of the career-ending fibrosis and muscle contracture. [112] Gastrocnemius tendon strain Autologous BMSCs; intralesional; 20 × 106 cells 1 dog No At 30, 60, 90, 180, and 365 days; successful functional outcome; incomplete healing with serial orthopedic and ultrasound examinations [118] Hip dysplasia Autologous SVF (2–5 × 106 cells) or allogeneic AD-MSCs (2–8 × 105 cells); acupuncture point injection 5 dogs in MSC group; 4 dogs in SVF group No At 7, 15, and 30 days; clear improvement was observed in both groups. [24] SVF, stromal vascular fraction; PRGF, plasma rich in growth factors; AD-MSC, adipose tissue-derived mesenchymal stem cell; MSC, mesenchymal stem cell; BMSC, bone-marrow-derived mesenchymal stem cell; OA, osteoarthritis. The utility of stem cells in musculoskeletal disease has been actively studied in humans, and preclinical study results using animal models provide useful information for the clinical applications of stem cells in animal disease. The clinical relevance of some disease has been identified, but the pathophysiology, disease process, and treatment responses could vary between species. In addition, preclinical animal study results were overstated due to inappropriate controls and different evaluation methods. Thus, human study results cannot be applied directly to animals, and further research is required. STEM CELL TRIALS IN NEOPLASIA According to a previous report [120], cytotoxic chemotherapy has been exploited for a variety of tumor treatments in small animal medicine. These chemotherapy regimens often have
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