The Effects Of FK506on Function And Revascularization Of Islet Grafts In Diabetic Mice

Background Remarkable progress has been made in islet transplantationover a span of40years. Once just an experimental curiosity in mice, thistherapy has moved forward, and can now provide robust therapy for highlyselected patients with type1diabetes, refractory to stabilization by othermeans. Currently, about1100patients have undergone islet transplantationat40international sites since the Edmonton Protocol was reported in2000.Islet transplantation has been criticized for the use of multiple donorpancreas organs to remain insulin independence rates. An research pointout that effective islet transplantation cost about$210837.10.It is promptedresearchers to search for the way to reduce islet transplantation donor organneeded. For example, intervention of avoid instant blood-mediatedinflammatory reaction (IBMIR), to explore more ideal graft-sites, toimprove immunosuppressant scheme, to promote the revascularization afterislet transplantation.Objective To investigate the effects of FK506on function andrevascularization of transplanted islets after pancreatic islet transplantation (PIT) in diabetic mice.Methods Pancreatic islets of donor mice were obtained by infusion ofcollagenase P solution with pancreatic duct and Ficoll-400density gradientcentrifugation, then transplanted into renal capsule of type I diabetes mice.The recipients were divided into two groups: control group（PIT group)and FK506-treated group (PIT+FK506group). The blood glucose ofrecipient mice after islet transplantation was monitored. The histologicalfeature, function of insulin secretion, and revascularization of the graftswere observed.Results The blood glucose on each time point had no significantdifferences between PIT group and PIT+FK506group(P>0.05).Histological examination showed that all the islet grafts survivedwell and had no difference. On day3~5and20after transplantation,compared to PIT group, VEGF and CD34expressions were significantlylower in PIT+FK506group. On day3~5and20after transplantation, thenewly-formed microvascular density of renal subcapsular islet grafts posttransplantation in PIT+FK506group(9.3±1.0and61.0±2.7) weresignificantly lower than those in PIT group (16.6±1.3and96.7±2.3)(P<0.05).Conclusion In the period of angiogenesis, the therapeutic dose of FK506inhibits the revascularization of transplanted pancreatic islets, but does notaffect the insulin secretion of the transplanted grafts directly.