Companion animals: Translational scientist’s new best friends

Kol, Amir; Arzi, Boaz; Athanasiou, Kyriacos A.; Farmer, Diana L.; Nolta, Jan A.; Rebhun, Robert B.; Chen, Xinbin; Griffiths, Leigh G.; Verstraete, Frank J.M.; Murphy, Christopher J.; Borjesson, Dori L.

doi:10.1126/scitranslmed.aaa9116

Cited by 157 publications

(183 citation statements)

References 61 publications

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“…These diseases in companion animals may better reflect the complex genetic, environmental, and physiological variations present in human diseases compared to induced diseases in laboratory animals [20]. Clinical trials in academic veterinary medicine mirror that of human healthcare systems, and animal owners are eager to enroll in these trials [20].…”

Section: Introductionmentioning

confidence: 99%

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome

Clark

Fierro

et al. 2017

Stem Cell Res Ther

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BackgroundAdipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome.MethodsHuman and feline ASCs were evaluated for phenotype, immunomodulatory profile, and transcriptome. Additionally, transwells were used to determine the role of cell-cell contact in ASC-mediated inhibition of lymphocyte proliferation in both humans and cats.ResultsSimilar to human ASCs, feline ASCs were highly proliferative at low passages and fit the minimal criteria of multipotent stem cells including a compatible surface protein phenotype, osteogenic capacity, and normal karyotype. Like ASCs from all species, feline ASCs inhibited mitogen-activated lymphocyte proliferation in vitro, with or without direct ASC-lymphocyte contact. Feline ASCs mimic human ASCs in their mediator secretion pattern, including prostaglandin E2, indoleamine 2,3 dioxygenase, transforming growth factor beta, and interleukin-6, all augmented by interferon gamma secretion by lymphocytes. The transcriptome of three unactivated feline ASC lines were highly similar. Functional analysis of the most highly expressed genes highlighted processes including: 1) the regulation of apoptosis; 2) cell adhesion; 3) response to oxidative stress; and 4) regulation of cell differentiation. Finally, feline ASCs had a similar gene expression profile to noninduced human ASCs.ConclusionsFindings suggest that feline ASCs modulate lymphocyte proliferation using soluble mediators that mirror the human ASC secretion pattern. Uninduced feline ASCs have similar gene expression profiles to uninduced human ASCs, as revealed by transcriptome analysis. These data will help inform clinical trials using cats with naturally occurring diseases as surrogate models for human clinical trials in the regenerative medicine arena.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0528-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome

Clark

Fierro

et al. 2017

Stem Cell Res Ther

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“…Hence, surgical joint destabilization is the most frequently employed model. Although the value of these rapidly changing rodent OA models should not be underestimated, naturally occurring disease in companion animals more closely reflects the complex genetic, physiological and environmental variations that occur in human OA 9,10 .…”

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confidence: 99%

“…Academic and private practice veterinary medicine can provide valuable biomedical research data, as referral centres are often equipped with MRI and CT scanners, arthroscopes and state-of-theart pathology and molecular diagnostic capabilities. Academic veterinary centres also pilot advances in the use of anti-inflammatory and pain-modulating OA drug therapies 10,14,15 . In this Review, we summarize research relating to common forms of spontaneous dog OA, focusing on the presentation and genetics of analogous diseases of the hip and knee, within a framework of human OA phenotypes.…”

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confidence: 99%

Spontaneous dog osteoarthritis — a One Medicine vision

et al. 2019

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| 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.

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“…Nonetheless, a study of naturally occurring diseases is superior to the study of induced disease in rodent models. 49 The number of dogs included in our study was relatively small, although comparable to numbers typically seen in published rodent model studies. The variability that existed among the dogs included in the study, and the relatively small number of animals studied, render some of the statistical comparisons underpowered, increasing the likelihood of type II error.…”

Section: Discussionmentioning

confidence: 56%

“…Moreover, variability existed in medical interventions administered to control secondary hyperparathyroidism (e.g., phosphorous binders). Nonetheless, a study of naturally occurring diseases is superior to the study of induced disease in rodent models . The number of dogs included in our study was relatively small, although comparable to numbers typically seen in published rodent model studies.…”

Section: Discussionmentioning

confidence: 75%

The Influence of Chronic Kidney Disease on the Structural and Mechanical Properties of Canine Bone

Shipov

Shahar

Sugar

et al. 2017

Veterinary Internal Medicne

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BackgroundChronic kidney disease (CKD) is common in companion animals. Secondary hyperparathyroidism is an inevitable consequence of the disease and may have deleterious effect on the bone; however, the information regarding CKD‐associated bone abnormalities in companion animals is scarce.Hypothesis/ObjectivesDogs with CKD have decreased bone quality compared to dogs without CKD.AnimalsNine dogs diagnosed with naturally occurring CKD for at least 6 months and 9 age‐matched controls.MethodsDogs with CKD were enrolled and compared to 9 age‐, weight‐, and sex‐matched control dogs with no evidence of CKD. Samples were assessed using light microscopy, mechanical testing, and microcomputed tomography. Variables evaluated included microstructural features such as number, size, and density of Haversian canals, resorption cavities and osteocytic lacunae, bone mineral density, porosity and Young's modulus.ResultsMedian lacunae size was significantly smaller in the CKD group compared to the control group (P = 0.001). Resorption cavity density was higher in the CKD compared to the control group (10 [8–14] vs. 7 [4–9]/mm2, respectively, P = 0.001). Overall porosity was significantly (2.3‐fold) higher in the CKD compared to the control group. There was no difference in Young's moduli between groups.Conclusions and Clinical ImportanceNaturally occurring CKD affects bone quality in dogs, but these changes are relatively mild and likely not to be manifested clinically. The duration of the disease in dogs evaluated here is short compared to cats and human patients, likely accounting for the more subtle changes in dogs compared to other species.

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Companion animals: Translational scientist’s new best friends

Cited by 157 publications

References 61 publications

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome

Spontaneous dog osteoarthritis — a One Medicine vision

The Influence of Chronic Kidney Disease on the Structural and Mechanical Properties of Canine Bone

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