Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Cell Transplant. 2014 Mar;23(3):273-83. doi: 10.3727/096368912X661364. Epub 2013 Jan 2.
Early graft loss in islet transplantation means that a large amount of donor islets is required. Endothelial cells and endothelial colony-forming cells (ECFCs) have been reported to improve instant blood-mediated inflammatory reaction (IBMIR) in vitro. In this study, we examined if ECFC-coated porcine islets would prevent early graft loss in vivo. Human ECFCs were prepared from cord blood and cocultured with islets to make composite grafts. Diabetic nude mice underwent intraportal transplantation. Blood glucose levels were monitored, and morphological examination of the grafts along with analysis of the components of IBMIR and inflammatory reaction were performed with the liver tissues. The ECFC-coated islets significantly decreased blood glucose levels immediately after transplantation compared to the uncoated islets. Composite ECFC islet grafts were observed in the liver sections, associated with a more insulin(+) area compared to that of the uncoated group within 48 h after transplantation. Deposition of CD41a, C5b-9, and CD11b(+) cells was also decreased in the ECFC-coated group. Expression of porcine HMGB1 and mouse TNF-α was increased in the transplantated groups compared to the sham operation group, with a trend of a decreasing trend across the uncoated group, the ECFC-coated group, and the sham group. We demonstrated that the composite ECFC porcine islets transplanted into the portal vein of nude mice improved early graft loss and IBMIR in vivo.
胰岛移植早期移植物失功意味着需要大量供体胰岛。有报道称内皮细胞和内皮祖细胞(ECFCs)可改善体外即时血介导的炎症反应(IBMIR)。在这项研究中,我们研究了 ECFC 包被的猪胰岛是否可以预防体内早期移植物失功。从脐血中分离出人 ECFCs 并与胰岛共培养,制成复合移植物。糖尿病裸鼠门静脉内移植。监测血糖水平,并对移植后肝组织进行形态学检查,分析 IBMIR 成分和炎症反应。与未包被的胰岛相比,ECFC 包被的胰岛在移植后立即显著降低血糖水平。在移植后 48 小时内,肝组织切片中观察到 ECFC 胰岛复合移植物,与未包被组相比,胰岛素阳性面积更大。CD41a、C5b-9 和 CD11b(+)细胞的沉积在 ECFC 包被组中也减少。与假手术组相比,移植组猪 HMGB1 和鼠 TNF-α 的表达增加,未包被组、ECFC 包被组和假手术组呈下降趋势。我们证明,将复合 ECFC 猪胰岛门静脉内移植到裸鼠体内可改善体内早期移植物失功和 IBMIR。