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J. Vet. Sci. 2016; 17(4): 539-548  https://doi.org/10.4142/jvs.2016.17.4.539
Canine adipose tissue-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating T cells in rats
Hyun-Wook Kim1,2,†, Woo-Jin Song1,†, Qiang Li1, Sei-Myoung Han1, Kee-Ok Jeon1, Sang-Chul Park1, Min-Ok Ryu1, Hyung-Kyu Chae1, Kweon Kyeong1, Hwa-Young Youn1,*
1Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
2Haemaru Referral Animal Hospital, Seongnam 13590, Korea
Correspondence to: Hwa-Young Youn
Tel/Fax: +82-2-880-1266;
E-mail: hyyoun@snu.ac.kr
Received: March 24, 2016; Revised: April 1, 2016; Accepted: April 8, 2016; Published online: December 30, 2016.
Abstract
Severe acute pancreatitis (SAP) is associated with systemic complications and high mortality rate in dogs. Mesenchymal stem cells (MSCs) have been investigated for their therapeutic potential in several inflammation models. In the present study, the effects of canine adipose tissue-derived (cAT)-MSCs in a rat model of SAP induced by retrograde injection of 3% sodium taurocholate solution into the pancreatic duct were investigated. cAT-MSCs labeled with dioctadecyl-3,3,3’-tetramethylindo-carbocyanine perchlorate (1 × 107 cells/kg) were systemically administered to rats and pancreatic tissue was collected three days later for histopathological, quantitative real-time polymerase chain reaction, and immunocytochemical analyses. Greater numbers of infused cAT-MSCs were detected in the pancreas of SAP relative to sham-operated rats. cAT-MSC infusion reduced pancreatic edema, inflammatory cell infiltration, and acinar cell necrosis, and decreased pancreatic expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, -6, -12, -17, and -23 and interferon-γ, while stimulating expression of the anti-inflammatory cytokines IL-4 and IL-10 in SAP rats. Moreover, cAT-MSCs decreased the number of clusters of differentiation 3-positive T cells and increased that of forkhead box P3-positive T cells in the injured pancreas. These results indicate that cAT-MSCs can be effective as a cell-based therapeutic strategy for treatment of SAP in dogs.
Keywords: acute pancreatitis, anti-inflammatory agents, dogs, mesenchymal stromal cell, regulatory T-lymphocytes


© 2016 The Korean Society of Veterinary Science.