Human blood outgrowth endothelial cells improve islet survival and function when co-transplanted in a mouse model of diabetes
Human blood outgrowth endothelial cells improve islet survival and function when co-transplanted in a mouse model of diabetes
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DOI：
10.1007/s00125-012-2754-3
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发表时间：
2013-02-01
期刊：
影响因子：
8.2
通讯作者：
De Leu, N.
中科院分区：
文献类型：
--
作者：
Coppens, V.;Heremans, Y.;De Leu, N.
由于目前的胰岛移植方案遭受严重的移植物丢失和功能障碍，需要维持这种治疗的长期益处的策略。通过血管快速和充足的氧气和营养输送改善胰岛移植和功能。本报告评估了成人血液生长内皮细胞（BOEC）对胰岛移植物血管化和功能的潜在有益作用。将5 × 10（5）人BOEC与大鼠边缘胰岛移植物共同移植到高血压NOD严重联合免疫缺陷（SCID）小鼠的肾包膜下，并评估了对代谢结果的影响。尽管血管密度未受影响，胰岛与BOEC的联合移植导致血糖显着且特异性的改善和血浆C肽的增加。此外，与对照小鼠相比，BOEC受体显示出减少的β细胞死亡和体重、β细胞增殖和移植血管和β细胞体积的增加。体内细胞示踪证实BOEC保留在移植部位并且不扩增。潜在的临床适用性强调了共同移植胰岛与BOEC来自1型diabetes patient.The目前的数据支持使用自体BOEC的翻译研究，旨在改善目前的胰岛移植方案治疗脆性1型糖尿病的代谢的好处。
As current islet-transplantation protocols suffer from significant graft loss and dysfunction, strategies to sustain the long-term benefits of this therapy are required. Rapid and adequate oxygen and nutrient delivery by blood vessels improves islet engraftment and function. The present report evaluated a potentially beneficial effect of adult human blood outgrowth endothelial cells (BOEC) on islet graft vascularisation and function.Human BOEC, 5 x 10(5), were co-transplanted with a rat marginal-islet graft under the kidney capsule of hyperglycaemic NOD severe combined immunodeficiency (SCID) mice, and the effect on metabolic outcome was evaluated.Although vessel density remained unaffected, co-transplantation of islets with BOEC resulted in a significant and specific improvement of glycaemia and increased plasma C-peptide. Moreover, in contrast to control mice, BOEC recipients displayed reduced beta cell death and increases in body weight, beta cell proliferation and graft-vessel and beta cell volume. In vivo cell tracing demonstrated that BOEC remain at the site of transplantation and do not expand. The potential clinical applicability was underscored by the observed metabolic benefit of co-transplanting islets with BOEC derived from a type 1 diabetes patient.The present data support the use of autologous BOEC in translational studies that aim to improve current islet-transplantation protocols for the treatment of brittle type 1 diabetes.