Ye-In Oh

Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell-based interferon-β gene therapy and cisplatin in a mouse melanoma model

BACKGROUND AIMS Adipose tissue (AT)-derived mesenchymal stromal cells (MSC) (AT-MSC) represent a novel tool for delivering therapeutic genes to tumor cells. Interferon (IFN)-β is a cytokine with pleiotropic cellular functions, including anti-proliferative, immunomodulatory and anti-angiogenic activities. The purpose of this study was to engineer canine AT-MSC (cAT-MSC) producing IFN-β and to evaluate the anti-tumor effect of cAT-MSC-IFN-β combined with cisplatin in mouse melanoma model. METHODS cAT-MSC engineered to express mouse IFN-β were generated using a lentiviral vector (cAT-MSC-IFN-β) and the secreted IFN-β-induced inhibition of tumor cell growth and apoptosis on B16F10 cells was investigated in vitro prior to in vivo studies. Melanoma-bearing mouse was developed by injecting B16F10 cells subcutaneously into 6-week-old C57BL/6 mice. After 14 days, cisplatin (10 mg/kg) was injected intratumorally, and 3 days later the engineered cAT-MSC were injected subcutaneously every 3 days to death. Tumor volume and survival times were measured. RESULTS The combination treatment of cAT-MSC-IFN-β with cisplatin was more effective in inhibiting the growth of melanoma and resulted in significantly extended survival time than both an unengineered cAT-MSC-cisplatin combination group and a cisplatin-alone group. Interestingly, subcutaneously injected cAT-MSC-IFN-β were migrated to tumor sites. CONCLUSIONS Our data suggest that canine AT-MSC could serve as a powerful cell-based delivery vehicle for releasing therapeutic proteins to tumor lesions. Maximal anti-tumor effects were seen when this therapy was combined with a DNA-damaging chemotherapeutic agent. This study demonstrates the possible applicability of AT-MSC-mediated IFN-β in treating canine and human cancer patients.

Use of laparoscopy for diagnosing experimentally induced acute pancreatitis in dogs

Diagnosis of acute pancreatitis in dogs remains a significant challenge despite the development of advanced diagnostic methodologies. Visual inspection and pancreas biopsy using laparoscopy are generally considered to be procedures free of complications when conducted on healthy animals. However, the usefulness of laparoscopy for diagnosing acute pancreatitis has not been assessed. In the present study, the efficacy of laparoscopy for diagnosing acute pancreatitis in dogs was evaluated in animals with experimentally induced acute pancreatitis. Gross appearance of the pancreatic area was examined by laparoscopy to survey for the presence of edema, adhesions, effusion, pseudocysts, hemorrhage, and fat necrosis. Laparoscopic biopsy was performed and the histopathologic results were compared to those of pancreatic samples obtained during necropsy. The correlation between laparoscopy and histopathologic findings of the pancreas was evaluated. The presence of adhesions, effusion, and hemorrhage in the pancreatic area observed by laparoscopy significantly correlated with the histopathologic results (p < 0.05). There was no significant relationship between the histopathologic and laparoscopic biopsy findings. Results of this study suggested that laparoscopic evaluation of gross lesions has clinical significance although the laparoscopic biopsy technique has some limitations. This method combined with additional diagnostic tools can be effective for diagnosing acute pancreatitis in dogs.