CTLA4 overexpressing adipose tissue-derived mesenchymal stem cell therapy in a dog with steroid-refractory pemphigus foliaceus.

BACKGROUND: Canine pemphigus foliaceus is an autoimmune antibody-mediated skin disease characterized by acantholysis. The objective of this case report is to present the successful management of steroid refractory pemphigus foliaceus with cytotoxic T-lymphocyte antigen 4 (CTLA4)-overexpressing adipose tissue mesenchymal stem cells (ATMSCs). CASE PRESENTATION: A 10-year-old, 12.3-kg, castrated male Shih Tzu presented with severe pruritus and anorexia. The diagnosis of pemphigus foliaceus was made based on its history, physical examination, and histopathology results of a skin biopsy. Treatment with prednisolone and combination therapy of other immunosuppressive drugs had failed; therefore, immunosuppressive gene, CTLA4 overexpressing ATMSCs (CTLA4-ATMSCs) and/or naive ATMSCs administration was performed with the consent of the owner. ATMSCs were administered 21 times over a period of 20 months with intervals of 2 to 8 week. Prednisolone was gradually tapered concurrently and no relapse of the clinical signs was observed. After the termination of CTLA4-ATMSCs and/or naive ATMSCs treatment, the skin lesions had improved and could be managed with a low dose of prednisolone for 12 months. CONCLUSION: CTLA4-ATMSCs or naive ATMSCs transplantation may be beneficial as adjunctive therapy to initiate and maintain the remission of skin lesions caused by pemphigus foliaceus in veterinary medicine.

Accidental afloqualone intoxication in two dogs.

Two dogs presented to the emergency service after accidental ingestion of afloqualone tablets, a muscle relaxant used for back pain in humans. Toxic effects of the drug in these dogs included vomiting, respiratory depression, seizures, ataxia, bradycardia, and hematuria. Treatment consisted of fluid diuresis, furosemide, and propofol. Flumazenil, a gamma-amino butyric acid antagonist, was administered intravenously; however, it was not effective in stopping the seizures in these dogs. Both dogs recovered with supportive treatment. To the authors' knowledge, this is the first documented report of afloqualone intoxication in dogs.

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)-1ß, -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.