Abstract
The objective of the present study was to investigate the effects of mesenchymal stem cells (MSCs) genetically modified by lentivirus-mediated mouse interleukin-12 (Lenti-mIL-12) in treating malignant ascites in mice. The in vitro chemotactic effect of Lenti-mIL-12-MSC culture supernatant on dendritic cells was investigated using a chemotaxis chamber. Liver cancer H22 and MethA ascites models were constructed. Mice were divided evenly into four groups: Normal saline, MSC, Null and Lenti-mIL-12-MSC. The survival rate, ascites volume and red blood cell number were measured for these groups. The toxicity and side effects of Lenti-mIL-12-MSCs were investigated using visual and microscopy inspections. The results indicated that mIL-12 had a strong chemotactic effect on dendritic cells. mIL-12 was highly expressed in ascites of Lenti-mIL-12-MSC-treated mice. Lenti-mIL-12-MSCs reduced the volume of ascites and the number of red blood cells in ascites and thus increased the survival rate and prolonged the survival duration of the mice. Furthermore, Lenti-mIL-12-MSCs showed no toxicity and side effects on the mice with malignant ascites. In conclusion, the results demonstrated that Lenti-mIL-12-MSCs inhibited the growth of ascites and promoted the survival of tumor-bearing mice, suggesting that Lenti-mIL-12-MSCs exerts a therapeutic effect on malignant ascites by stimulating the immune responses of the mice.
Highlights
Malignant ascites, a common complication of abdominal malignancies, is one of the main causes of mortality in patients with cancer
To assess the chemotactic effect of mouse interleukin (mIL)‐12 on dendritic cells, the number of dendritic cells that migrated through the PVP membrane in the chemotaxis chamber was counted under the microscope following Wright‐Giemsa's staining
The average number of cells that passed through the PVP membrane and were counted under each high magnification field was 8±0.4 for the NS group, 14±0.9 for the mesenchymal stem cells (MSCs) group, 12±0.8 for the Null group and 43±2.4 for the Lenti‐mIL‐12‐MSC group (Fig. 1A)
Summary
A common complication of abdominal malignancies, is one of the main causes of mortality in patients with cancer. The treatment of malignant ascites is important for improving the prognosis of abdominal malignancies. There are numerous methods for the treatment of malignant ascites; at present, the frequently used methods include intraperitoneal chemotherapy, intraperitoneal injection of radioisotopes or biological response modifiers, systemic chemotherapy and radiotherapy [1,2,3]. Effective therapies remain lacking, and existing problems include short efficacy and drug resistance, as well as questions on how to maintain high levels of abdominal local drug concentration. It is important to select an improved therapy carrier to limit IL-12 entering the tumor tissue and to maintain its therapeutic dose for tumor therapy. Mesenchymal stem cells play an important role in the targeted release of therapeutic gene expression products into the tumor tissue to inhibit tumor growth and metastasis. Using MSCs as the targeted vehicle of gene therapy, the anti‐ascites effect of lentivirus‐mediated mIL‐12 MSCs (Lenti‐mIL‐12‐MSCs) was explored
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