A preclinical evaluation of alternative site for islet allotransplantation.
A preclinical evaluation of alternative site for islet allotransplantation.
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同种异体胰岛移植替代位点的临床前评估
DOI：
10.1371/journal.pone.0174505
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Wang C;Du X;He S;Yuan Y;Han P;Wang D;Chen Y;Liu J;Tian B;Yang G;Yi S;Gao F;Zhong Z;Li H;Cheng J;Lu Y
骨髓腔(BMC)最近被确定为肝脏的胰岛移植的替代部位。本研究旨在比较糖尿病猴的骨髓基质细胞和肝脏作为同种异体胰岛移植的部位。用链脲佐菌素诱导猕猴糖尿病模型，随机分为3组：1组(胰岛移植加免疫抑制剂)、2组(胰岛移植于胫骨BMC内)、3组(胰岛移植于胫骨BMC内)。术前测定C-肽和血糖水平。静脉葡萄糖耐量试验(IVGTT)用于评估移植物的功能，全血细胞计数用于评估细胞数量的变化。用双抗体夹心法和MILLIPLEX法检测细胞因子的表达。移植后4个月，组3的5只猴胰岛素依赖时间显著延长(组1：78.219.0d；组2：58.8d±17.0d；组3：189.6±26.2d)，血浆C肽水平明显升高。输液程序与不良反应无关。移植后225天用双硫腙(DTZ)和胰岛素/胰高血糖素染色观察BMC中的功能性胰岛。我们的结果表明，移植到糖尿病恒河猴BMC中的同种异体胰岛比移植到肝脏中的胰岛存活和功能保持的时间更长。这项研究首次成功地证明了同种异体胰岛植入非人灵长类动物的骨髓基质细胞(BMC)。
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).