Immunoselected STRO-3+ mesenchymal precursor cells reduce inflammation and improve clinical outcomes in a large animal model of monoarthritis.

BACKGROUND: The purpose of this study was to investigate the therapeutic efficacy of intravenously administered immunoselected STRO-3 + mesenchymal precursor cells (MPCs) on clinical scores, joint pathology and cytokine production in an ovine model of monoarthritis. METHODS: Monoarthritis was established in 16 adult merino sheep by administration of bovine type II collagen into the left hock joint following initial sensitization to this antigen. After 24 h, sheep were administered either 150 million allogeneic ovine MPCs (n = 8) or saline (n = 8) intravenously (IV). Lameness, joint swelling and pain were monitored and blood samples for leukocytes and cytokine levels were collected at intervals following arthritis induction. Animals were necropsied 14 days after arthritis induction and gross and histopathological evaluations were undertaken on tissues from the arthritic (left) and contralateral (right) joints. RESULTS: MPC-treated sheep demonstrated significantly reduced clinical signs of lameness, joint pain and swelling compared with saline controls. They also showed decreased cartilage erosions, synovial stromal cell activation and angiogenesis. This was accompanied by decreased infiltration of the synovial tissues by CD4+ lymphocytes and CD14+ monocytes/macrophages. Over the 3 days following joint arthropathy induction, the numbers of neutrophils circulating in the blood and plasma concentrations of activin A were significantly reduced in animals administered MPCs. CONCLUSIONS: The results of this study have demonstrated the capacity of IV-administered MPCs to mitigate the clinical signs and some of the inflammatory mediators responsible for joint tissue destruction in a large animal model of monoarthritis.

Association between hepatic histopathologic lesions and clinical findings in dogs undergoing surgical attenuation of a congenital portosystemic shunt: 38 cases (2000-2004).

OBJECTIVE: To review hepatic histopathologic lesions in dogs undergoing surgical attenuation of a congenital portosystemic shunt (CPSS) in relation to clinical findings and tolerance of complete surgical attenuation. DESIGN: Retrospective case series. ANIMALS: 38 dogs that underwent surgical attenuation of a CPSS. PROCEDURES: Hepatic histologic examination findings and medical records of dogs undergoing surgical attenuation of a single CPSS between August 2000 and July 2004 were reviewed. Liver biopsy specimens were obtained from 38 dogs during surgery prior to complete (n = 16) or partial (22) attenuation of a CPSS and from 13 of the same dogs a median of 3 months following surgical attenuation. RESULTS: Portal tracts were inadequate for interpretation in 2 liver biopsy specimens. Liver biopsy specimens obtained prior to surgical attenuation of a CPSS had a lack of identifiable portal veins (13/36 dogs), hepatic arteriolar proliferation (25/36), ductular reaction (5/36), steatosis (16/38), and iron accumulation (32/38). Lack of identifiable portal veins on histologic examination was associated with increased hepatic arteriolar proliferation, decreased tolerance to complete surgical CPSS attenuation, and decreased opacification of intrahepatic portal vessels on portovenography. Ductular reaction was always associated with failure to tolerate complete surgical attenuation of a CPSS. Surgical CPSS attenuation resulted in significant clinical, serum biochemical, and portovenographic changes indicative of improved liver function, but only subtle changes in hepatic histologic examination findings. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs without identifiable intrahepatic portal veins that had a ductular reaction on hepatic histologic examination were less likely to tolerate complete attenuation of a CPSS.