Intravenous injection of adipose-derived mesenchymal stromal cells benefits gait and inflammation in a spontaneous osteoarthritis model.

Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression. Indeed, multiple manuscripts have evaluated intra-articular administration of adMSCs as a therapeutic; however, comparatively few evaluations of systemic delivery methods have been published. Therefore, the aim of this study was to evaluate the short-term impact of intravenous (IV) delivery of allogeneic adMSCs in an established model of spontaneous OA, the Hartley guinea pig. Animals with moderate OA received once weekly injections of 2 × 106 adMSCs or vehicle control for 4 weeks in peripheral veins; harvest occurred 2 weeks after the final injection. Systemic administration of adMSCs resulted in no adverse effects and was efficacious in reducing clinical signs of OA (as assessed by computer-aided gait analysis) compared to control injected animals. Further, there were significant decreases in key inflammatory mediators (including monocyte chemoattractant protein-1, tumor necrosis factor, and prostaglandin E2 ) both systemically (liver, kidney, and serum) and locally in the knee (joint tissues and synovial fluid) in animals treated with IV adMSCs relative to controls (as per enzyme-linked immunosorbent assay and/or immunohistochemistry, dictated by tissue sample). Thus, systemic administration of adMSCs by IV injection significantly improved gait parameters and reduced both systemic and intra-articular inflammatory mediators in animals with OA. These findings demonstrate the potential utility of alternative delivery approaches for cellular therapy of OA, particularly for patients with multiple affected joints.

Development of a microcomputed tomography scoring system to characterize disease progression in the Hartley guinea pig model of spontaneous osteoarthritis.

AIM: There is potential discrepancy between human and laboratory animal studies of osteoarthritis (OA), as radiographic assessment is the hallmark of the former and histopathology the standard for the latter. This suggests a need to evaluate OA in animal models in a manner similar to that utilized in people. Our study aimed to develop a whole joint grading scheme for microcomputed tomography (microCT) images in Hartley guinea pigs, a strain that recapitulates joint changes highlighted in human spontaneous OA. MATERIALS AND METHODS: Knees from animals aged 2, 3, 5, 9, and 15 months were evaluated via whole joint microCT and standard histologic scoring. Quantitative microCT parameters, such as bone volume/total volume were also collected. RESULTS: Both whole joint microCT and histologic scores increased with advancing age and showed strong correlation (r = 0.89. p < 0.0001). Histologic scores, which focus on cartilage changes, increased progressively with age. Whole joint microCT scores, which characterize bony changes, followed a stepwise pattern: scores increased between 3 and 5 months of age, stayed consistent between 5 and 9 months, and worsened again between 9 and 15 months. CONCLUSIONS: This work provides data that advocates the use of a whole joint microCT scoring system in guinea pig studies of OA, as it provides important information regarding bony changes that occur at a different rate than articular cartilage changes. This grading scheme, in conjunction with histology and quantitative microCT measurements, may enhance the translational value of this animal model as it pertains to human work.

Clinically healthy overweight and obese dogs differ from lean controls in select CBC and serum biochemistry values.

BACKGROUND: Obesity is a global disease, affecting nearly half a billion people. Unfortunately, this trend is mirrored in our canine population. OBJECTIVES: As obesity is a complex inflammatory disease, there is a need to determine whether routine medical screening tests may indicate, or be influenced by, its presence. The objective of the current study was to determine if significant differences exist between CBC and biochemical profile values from control vs overweight/obese, client-owned dogs considered clinically healthy. METHODS: Dogs presented for routine health examinations, including minor dental or elective surgical procedures, were retrospectively identified from a hospital population. Animals were allocated to 2 categories based on body condition score (BCS), and data were analyzed by Mann-Whitney nonparametric analysis with statistical significance at a P ≤ .05. RESULTS: After exclusions, 116 dogs were assigned to the overweight/obese group (BCS ≥ 7) and 240 dogs to the control group (BCS = 4-6). Overweight/obese dogs had higher total leukocyte counts and higher plasma protein and globulin concentrations. Other differences were attributed to decreased serum water fraction (increased sodium, albumin, calcium, and anion gap) in the overweight/obese group. Interestingly, chloride concentration was decreased (in the face of increased sodium) in the obese group. CONCLUSIONS: There is CBC and biochemical evidence to support the concern that obesity influences laboratory values, even in dogs considered clinically healthy. Prospective studies aimed at characterizing these changes are needed to provide insight into the connection between obesity and its comorbidities.

Hematology and biochemistry of aging-evidence of "anemia of the elderly" in old dogs.

BACKGROUND: Effects of aging on hematologic and biochemical variables are well described in people. Anemia of the elderly is attributed to iron deficiency, anemia of chronic disease, chronic kidney disease, myelodysplasia, or idiopathic causes. Limited studies have examined these variables in aging dogs, but they have typically examined single breeds in research settings. OBJECTIVE: The objective of this study was to identify differences in CBC and biochemistry values between adult and aged dogs of many breeds. METHODS: Dogs presenting for wellness examinations and minor dental/elective surgeries that were otherwise clinically healthy were retrospectively identified. Dogs were categorized by age: adult (1-7.9 years), senior (8-11.9 years), and geriatric (12+ years). Standard CBC and biochemistry data were collated. Asian breeds, Greyhounds, and dogs with data indicating overt underlying disease were excluded. The Kruskal-Wallis test was used to compare groups with statistical significance set at P ≤ .05. RESULTS: Hematocrit, MCV, and serum iron decreased with age, indicating possible iron-restricted erythropoiesis (IRE), due to iron deficiency or low-grade chronic inflammation. Total proteins, globulins, and platelet counts increased with age while albumin decreased, suggesting low-grade inflammation. Urea was increased in older dogs without a concurrent increase in creatinine, which points toward gastrointestinal bleeding or dehydration. CONCLUSION: Clinically healthy, aging dogs have changes in laboratory variables that indicate altered physiologies compared to younger adult animals, including evidence of IRE, inflammation, and potential gastrointestinal bleeding, suggesting a similar trend to that of elderly human beings. Future studies will examine markers of iron metabolism and inflammation in aging dogs.