Canine adipose tissue-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating T cells in rats.
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.
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.|Haemaru Referral Animal Hospital, Seongnam 13590, Korea.
Hyun-Wook
HW
Kim
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Woo-Jin
WJ
Song
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Qiang
Q
Li
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Sei-Myoung
SM
Han
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Kee-Ok
KO
Jeon
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Sang-Chul
SC
Park
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Min-Ok
MO
Ryu
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Hyung-Kyu
HK
Chae
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Kweon
K
Kyeong
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Hwa-Young
HY
Youn
D000208:Acute Disease; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D004285:Dogs; D007113:Immunity, Innate; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010195:Pancreatitis / Q000276:immunology / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology*
acute pancreatitis; anti-inflammatory agents; dogs; mesenchymal stromal cell; regulatory T-lymphocytes