title: Microencapsulated tumor assay: evaluation of the nude mouse model of pancreatic cancer.
abstract: OBJECTIVE
  To establish a more stable and accurate nude mouse model of pancreatic cancer using cancer cell microencapsulation.
  
  
  METHODS
  The assay is based on microencapsulation technology, wherein human tumor cells are encapsulated in small microcapsules (approximately 420 μm in diameter) constructed of semipermeable membranes. We implemented two kinds of subcutaneous implantation models in nude mice using the injection of single tumor cells and encapsulated pancreatic tumor cells. The size of subcutaneously implanted tumors was observed on a weekly basis using two methods, and growth curves were generated from these data. The growth and metastasis of orthotopically injected single tumor cells and encapsulated pancreatic tumor cells were evaluated at four and eight weeks postimplantation by positron emission tomography-computed tomography scan and necropsy. The pancreatic tumor samples obtained from each method were then sent for pathological examination. We evaluated differences in the rates of tumor incidence and the presence of metastasis and variations in tumor volume and tumor weight in the cancer microcapsules vs single-cell suspensions.
  
  
  RESULTS
  Sequential in vitro observations of the microcapsules showed that the cancer cells in microcapsules proliferated well and formed spheroids at days 4 to 6. Further in vitro culture resulted in bursting of the membrane of the microcapsules and cells deviated outward and continued to grow in flasks. The optimum injection time was found to be 5 d after tumor encapsulation. In the subcutaneous implantation model, there were no significant differences in terms of tumor volume between the encapsulated pancreatic tumor cells and cells alone and rate of tumor incidence. There was a significant difference in the rate of successful implantation between the cancer cell microencapsulation group and the single tumor-cell suspension group (100% vs 71.43%, respectively, P = 0.0489) in the orthotropic implantation model. The former method displayed an obvious advantage in tumor mass (4th wk: 0.0461 ± 0.0399 vs 0.0313 ± 0.021, t = -0.81, P = 0.4379; 8th wk: 0.1284 ± 0.0284 vs 0.0943 ± 0.0571, t = -2.28, respectively, P = 0.0457) compared with the latter in the orthotopic implantation model.
  
  
  CONCLUSIONS
  Encapsulation of pancreatic tumor cells is a reliable method for establishing a pancreatic tumor animal model.
authors.affiliation: Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital affiliated with to Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
authors.forename: Ming-Zhe
authors.initials: MZ
authors.lastname: Ma
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Cheng
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Ye
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jia-Xiang
authors.initials: JX
authors.lastname: Wang
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Shi
authors.forename: Bao-San
authors.initials: BS
authors.lastname: Han
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Peng
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured