Development of the Total Pancreatectomy and Autologous Islet Transplantation Models as the Step for Allogenic Islet Transplantation Experiments in the Swine

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Abstract

Background

Islet transplantation has been established as a treatment for type 1 diabetes mellitus (DM). However, there are some problems to overcome, such as the necessity of transplantation from multiple donors repeatedly and the difficulty of achievement of the long term insulin independence. Creating an experimental model with large animal is extremely important as a preclinical study aiming to overcome those problems. We successfully established the total pancreatectomy combined with autologous islet transplantation model in the swine.

Materials and Methods

Thirteen swine weighing 10-20 kg underwent total pancreatectomy under general anesthesia. [Experiment 1] Eight swine underwent only total pancreatectomy (TP group), and the results of body weight, fasting blood glucose (FBS) and intravenous glucose tolerance test (IVGTT) before and after total pancreatectomy were compared and analyzed. [Experiment 2] Five swine underwent total pancreatectomy, then 50% of the excised pancreas were isolated by Ricordi method. Isolated pancreatic islets were autologously transplanted from portal vein into the liver (Islet Tx group) and their postoperative data was compared with that of TP group.

Results

[Experiment 1] Loss of body weight was significantly severer (+0.8 kg vs -1.9 kg, p=0.032) in 7 days after total pancreatectomy than in 7 days before total pancreatectomy. The value of FBS (49.4 mg/dl vs 327.0 mg/dl, p=0.001)) and IVGTT 120 min (84.0 mg/dl vs 364.7 mg/dl, p=0.044) were increased significantly after total pancreatectomy. Insulin secretion after glucose injection was not detected in this series. [Experiment 2] Compared with TP group, the loss of body weight was mild (-1.9 kg vs -0.1 kg, p=0.22), and the survival rate was significantly increased (38% vs 100%, p=0.035) in Islet Tx group. The value of postoperative FBS (327.0 mg/dl vs 97.4 mg/dl, p=0.001) and IVGTT 120 min (364.7 mg/dl vs 153.5 mg/dl, p=0.016) were significantly lower in the Islet Tx group. In the Islet Tx group, insulin secretion after glucose injection was detected. This is because transplanted islets were survive and functioning. Pathological specimens on the 7th day after islet transplantation showed the engraftment of transplanted pancreatic islets into the intrahepatic portal vein.

Conclusions

We successfully established the insulin dependent DM model by using total pancreatectomy in the swine. We also successfully established the total pancreatectomy and islet autotransplantation model in the swine. Improvement in the outcomes of islet transplantation would be expected by developing this model to allogeneic islet transplantation experiments.

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