Allogeneic Pancreatic Islet Transplantation Into the Bone Marrow Cavity in Diabetic Rhesus Monkey

Abstract

Introduction: Liver is the general implantation site for clinical islet transplantation. but it has some disadvantages of physiologic and anatomic characterization for islet engraftment. Intraportal islet transplantation also has technical limitations and the risk of the instant blood-mediated inflammatory reaction (IBMIR) triggered by the islets. In recent years, bone marrow had been reported as an alternative site for islet transplantation in rats and mice. And these studies demonstrated that bone marrow cavity offers a widely distributed and well-vascularized microenvironment. In this study, we investigated whether the bone marrow cavity is a suitable site for islet transplantation in diabetic rhesus monkey. Methods: The monkey pancreas were digested with Collagenase P and purified by discontinued Ficoll density-gradient centrifugation. The glucose stimulated insulin secretion and cell viability of purified islets were assessed before transplantation. 3254±1140 IEQ/kg islets (5ml suspension) were transplanted into the bone marrow of 6 diabetic rhesus monkeys respectively through the medial tibial plateau. No immunosuppressant was used after transplantation. The recipients were evaluated by the following parameters: The general condition (body weight, food intake, behavioral activity, and etc.); Laboratory testing: blood biochemistry and routine blood examinations; and Glycemic control: fasting blood glucose (FBG), postprandial blood glucose (PBG). Results: Pancreatic islets can be successfully engrafted into the bone marrow of rhesus monkey. During the investigated 60 days, all the recipients were in good general health. Of the 6 receptors, 1 (17%) attained insulin independence with good glycemic control for 24 days, and little insulin dependence with good glycemic control until now; 5 (83%) reduced insulin dependence (18 vs. 6˜14 IU/day) with good glycemic control for mor than 45 days. Conclusions: These preliminary results show that, without immunosuppression treatment, the allogeneic islets can survive and remain functionally for a long period in bone marrow cavity in diabetic rhesus monkey. Further research the functional interaction between islet engraftment and bone marrow with nonhuman primate diabetic model, may provide experimental data for clinical application of bone marrow cavity islet transplant.Figure: [Extra Insulin Dose]Figure: [FBG Level]