Abstract
The bone marrow cavity (BMC) has recently been identified as an alternative site to the liver for islet transplantation. This study aimed to compare the BMC with the liver as an islet allotransplantation site in diabetic monkeys. Diabetes was induced in Rhesus monkeys using streptozocin, and the monkeys were then divided into the following three groups: Group1 (islets transplanted in the liver with immunosuppressant), Group 2 (islets transplanted in the tibial BMC), and Group 3 (islets transplanted in the tibial BMC with immunosuppressant). The C-peptide and blood glucose levels were preoperatively measured. An intravenous glucose tolerance test (IVGTT) was conducted to assess graft function, and complete blood cell counts were performed to assess cell population changes. Cytokine expression was measured using an enzyme-linked immune sorbent assay (ELISA) and MILLIPLEX. Five monkeys in Group 3 exhibited a significantly increased insulin-independent time compared with the other groups (Group 1: 78.2 ± 19.0 days; Group 2: 58.8 ± 17.0 days; Group 3: 189.6 ± 26.2 days) and demonstrated increases in plasma C-peptide 4 months after transplantation. The infusion procedure was not associated with adverse effects. Functional islets in the BMC were observed 225 days after transplantation using the dithizone (DTZ) and insulin/glucagon stains. Our results showed that allogeneic islets transplanted in the BMC of diabetic Rhesus monkeys remained alive and functional for a longer time than those transplanted in the liver. This study was the first successful demonstration of allogeneic islet engraftment in the BMC of non-human primates (NHPs).
Highlights
Allogeneic islet transplantation has been considered a potential treatment for type 1 diabetes mellitus (T1DM) [1],and islet and kidney co-transplantation could prolong the survival of kidney grafts, especially for TIDM patients with end-stage renal disease [2, 3].Various anatomical sites have been reported for islet transplantation, among which the liver has been primarily and widely used for clinical islet transplantation[4, 5]
Islets transplanted into the bone marrow cavity (BMC) could reverse hyperglycemia and exerted better glycemic control than those transplanted in the liver
We are the first group to demonstrate that transplanting islets in the BMCs of diabetic non-human primates (NHPs) reversed diabetes
Summary
Allogeneic islet transplantation has been considered a potential treatment for type 1 diabetes mellitus (T1DM) [1],and islet and kidney co-transplantation could prolong the survival of kidney grafts, especially for TIDM patients with end-stage renal disease [2, 3].Various anatomical sites have been reported for islet transplantation, among which the liver has been primarily and widely used for clinical islet transplantation[4, 5]. The instant blood-mediated inflammatory reaction is an innate immune response that causes significant islet graft loss[7,8,9]. Multiple factors lead to the loss of islet grafts, including high glucose levels, insufficient oxygen levels and high concentrations of drugs in the liver. The physiological and anatomical characteristics of the liver may cause the death of transplanted islets, and technical obstacles have been associated with the addition of sufficient islets to the portal circulation[10,11,12]. The infusion of islets into the portal system increased the portal pressure, which substantially reduces the viability of the transplanted islets
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