Division of Pediatric Endocrinology, Pediatric Diabetes Center and Islet Transplant Laboratory, Department of Pediatrics, Loma Linda University School of Medicine, 11175 Campus Street, Coleman Pavilion, A1120R, Loma Linda, CA 92354, United States.
World J Gastroenterol. 2010 Mar 14;16(10):1215-20. doi: 10.3748/wjg.v16.i10.1215.
To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.
Streptozotocin induced diabetic BALB/c mice were transplanted syngeneically under the kidney capsule with the following: (1) 200 islets (islet group: n = 12), (2) 1-5 x 10(6) bone marrow cells (bone marrow group: n = 11), (3) 200 islets and 1-5 x 10(6) bone marrow cells (islet + bone marrow group: n = 13), or (4) no cells (sham group: n = 5). All mice were evaluated for blood glucose, serum insulin, serum nerve growth factor (NGF) and glucose tolerance (GTT) up to postoperative day (POD) 14. Histological assessment for insulin, von Willebrand factor (vWF) and NGF was performed at POD 3, 7 and 14.
Blood glucose level was lowest and serum insulin was highest in the islet + bone marrow group. Serum NGF increased in islet, bone marrow, and islet + bone marrow groups after transplantation, and there was a significant difference (P = 0.0496, ANOVA) between the bone marrow and sham groups. The number of vessels within the graft area was significantly increased in both the bone marrow and islet + bone marrow groups at POD 14 as compared to the islet alone group (21.2 +/- 3.6 in bone marrow, P = 0.01, vs islet group, 22.6 +/- 1.9 in islet + bone marrow, P = 0.0003, vs islet group, 5.3 +/- 1.6 in islet-alone transplants). NGF was more strongly expressed in bone marrow cells compared with islets.
Bone marrow cells produce NGF and promote angiogenesis. Islet co-transplantation with bone marrow is associated with improvement of islet graft function.
阐明骨髓细胞促进移植胰岛周围血管生成的机制。
链脲佐菌素诱导的糖尿病 BALB/c 小鼠在肾包膜下进行同种异体移植，具体分组如下：（1）200 个胰岛（胰岛组：n=12），（2）1-5×10(6)骨髓细胞（骨髓组：n=11），（3）200 个胰岛和 1-5×10(6)骨髓细胞（胰岛+骨髓组：n=13），或（4）无细胞（假手术组：n=5）。所有小鼠在术后第 14 天进行血糖、血清胰岛素、血清神经生长因子（NGF）和葡萄糖耐量（GTT）评估。术后第 3、7 和 14 天进行胰岛素、血管性血友病因子（vWF）和 NGF 的组织学评估。
在胰岛+骨髓组中，血糖水平最低，血清胰岛素水平最高。移植后，胰岛、骨髓和胰岛+骨髓组的血清 NGF 增加，骨髓组和假手术组之间存在显著差异（P=0.0496，方差分析）。与单纯胰岛组相比，骨髓组和胰岛+骨髓组在术后第 14 天移植物区域内的血管数量明显增加（骨髓组为 21.2±3.6，P=0.01，与胰岛组相比，胰岛+骨髓组为 22.6±1.9，P=0.0003，与胰岛组相比，胰岛单独移植组为 5.3±1.6）。与胰岛相比，骨髓细胞中 NGF 的表达更强。
骨髓细胞产生 NGF 并促进血管生成。与单独胰岛移植相比，胰岛与骨髓共移植与胰岛移植物功能的改善相关。
