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Christopher M. Reilly, Shin Ae Park, Joshua A. Wood, Dori L. Borjesson, Christopher J. Murphy; Histologic Safety Of Peri-ocular Injection Of Allogeneic, Adipose Derived Mesechymal Stem Cells In Healthy Dogs. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2360.
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To evaluate the local and systemic histologic safety of allogeneic, adipose derived mesenchymal stem cells injected periocularly in healthy dogs.
6 healthy, young adult female purpose bred beagle dogs were used. All methods were in accordance with local IACUC approval. Adipose was harvested and mesenchymal stem cells (MSCs) were identified with fluorescence assisted flow cytometry, and confirmed stem cells were labeled with the fluorescent marker DiD. 3 dogs received 2 x 106 DiD-labeled adipose tissue derived canine MSCs and three dogs received unlabeled MSCs adjacent to the right third eyelid gland and adjacent to the lacrimal gland once weekly for 6 weeks. All dogs received vehicle only (DPBS) on the left weekly. Three weeks after the final injection, dogs were humanely euthanized, with complete gross and histopathologic evaluations of injected sites as well as all major organs. Lacrimal tissue inflammation was scored by a masked pathologist on a 4-pt scale (0 = no inflammation, 3 = severe inflammation), and was classified by cell type. Immunohistochemistry for T-cell (CD3) and B-cell (CD20) antigens was performed and enumerated on a similar 4-point scale. Inflammation scores were compared between all-MSC and vehicle, labeled and vehicle, and unlabeled and vehicle with the Wilcoxon rank sum test. Clinical and fluorescent analysis is presented elsewhere.
Inflammation scores for lacrimal and third eyelid glands are shown in Table 1 as mean +/- standard deviation. There was no significant difference between any group. One lacrimal gland injected with labeled MSCs had regionally moderate, T-cell rich inflammation that was not clinically or statistically significant. There were no significant, treatment-related systemic lesions in any dog. However, all dogs had a mild, eosinophil-rich extramedullary hematopoiesis in lymph nodes and splenic tissue.
Our results suggest that periocular allogeneic, adipose derived MSCs are safe for periocular injection in healthy dogs. Dogs spontaneously develop dry eye syndromes, and may be a translational model for testing clinical efficacy of MSCs for dry eye syndromes in humans.
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