Immune Modification Of MPEG In Homogeneous Islet Transplantation

Objective:To investigate the insulin secretion changes of rat islets after immune modification of methoxy-polyethylene glycol(mPEG5000); To investigate the impact and mechanisms of mPEG on islets survival in homogeneous rat islet transplantation..Methods:The islets Isolated from Wistar rats were divided into control group and mPEG-treated groups(with 200,300,400g/L mPEG, respectively), After culture for 24 h, the viability of islets was detected by dithizone staining, and insulin secretion function was examined by glucose stimulation test .The islets from different groups were mixed with splenic lymphocyte from SD rats to evaluate the immunogenicity .Negative control islets were not treated, treated islet were packed by mPEG , which were both implanted into the right lower muscle of the diabetes SD rat model, blank control were infused sodium chloride in the same site. To monitor the change of plasma glucose and insulin secretion, to detect the survival of the transplanted islets by pathological sections, and to detect immunological rejection by mixed lymphocyte culture.Results:The viability of islets or the insulin secretion function in three treated groups was not significantly different from that in the control group. However, the cytoxicity rates in mPEG-treated groups were markedly lower than those in the control groups (24.7%,14.8%,21.4% vs 69.5%,t=2.378,2.584,2.472,all P < 0.05). Furthermore, the cytoxicity in the islets treated with 300g/L mPEG was the lowest(14.8% vs 24.7%,21.4%, t=2.285,2.383,both P< 0.05). The survival time of mPEG-packed group were significantly prolonged (75.8±4.5d vs 7.2±1.1d,P<0.05), immunohistochemical stain expressed strong positive, but the transplantation place of negative control group could only be seen a few positive granules. And lymphocyte stimulation indices of mPEG-packed group were obviously lower (1.27±0.22 vs 3.78±0.32,P<0.05).Conclusion:mPEG can effectively mask the immunogenicity of rat islets while hardly affect the viability and insulin secretion; mPEG-packed rat islets survival can be effectively prolonged comparing to non-grafted islets, And the possible mechanism was related with immune modification.