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胰腺微环境对移植胰岛血管生成的有益作用。

Beneficial role of pancreatic microenvironment for angiogenesis in transplanted pancreatic islets.

作者信息

Lau Joey, Kampf Caroline, Mattsson Göran, Nyqvist Daniel, Köhler Martin, Berggren Per-Olof, Carlsson Per-Ola

机构信息

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.

出版信息

Cell Transplant. 2009;18(1):23-30. doi: 10.3727/096368909788237131.

DOI:10.3727/096368909788237131
PMID:19476206
Abstract

Pancreatic islets implanted heterotopically (i.e., into the kidney, spleen, or liver) become poorly revascularized following transplantation. We hypothesized that islets implanted into the pancreas would become better revascularized. Islets isolated from transgenic mice expressing enhanced yellow fluorescent protein (EYFP) in all somatic cells were cultured before they were implanted into the pancreas or beneath the renal capsule of athymic mice. Vascular density was evaluated in histological sections 1 month posttransplantation. EYFP was used as reporter for the transgene to identify the transplanted islets. Islet endothelial cells were visualized by staining with the lectin Bandeiraea simplicifolia (BS-1). Capillary numbers in intrapancreatically implanted islets were only slightly lower than those counted in endogenous islets, whereas islets implanted beneath the renal capsule had a markedly lower vascular density. In order to determine if this high graft vascular density at the intrapancreatic site reflected expansion of remnant donor endothelial cells or increased ingrowth of blood vessels from the host, also islets from Tie2-green fluorescent protein (GFP) mice (i.e., islets with fluorescent endothelial cells) were transplanted into the pancreas or beneath the renal capsule of athymic mice. These islet grafts revealed that the new vascular structures formed in the islet grafts contained very few GFP-positive cells, and thus mainly were of recipient origin. The reason(s) for the much better ingrowth of blood vessels at the intrapancreatic site merits further studies, because this may help us form strategies to overcome the barrier for ingrowth of host vessels also into islets in heterotopic implantation sites.

摘要

异位(即植入肾脏、脾脏或肝脏)移植的胰岛在移植后血管重建较差。我们推测,植入胰腺的胰岛血管重建会更好。从在所有体细胞中表达增强型黄色荧光蛋白(EYFP)的转基因小鼠分离出的胰岛,在植入无胸腺小鼠的胰腺或肾被膜下之前进行培养。移植后1个月,在组织学切片中评估血管密度。EYFP用作转基因的报告基因以识别移植的胰岛。通过用单叶豆凝集素(BS-1)染色来观察胰岛内皮细胞。胰腺内植入的胰岛中的毛细血管数量仅略低于内源性胰岛中的数量,而植入肾被膜下的胰岛血管密度明显较低。为了确定胰腺内移植部位的高移植血管密度是否反映了残余供体内皮细胞的扩张或宿主血管向内生长的增加,还将来自Tie2-绿色荧光蛋白(GFP)小鼠的胰岛(即具有荧光内皮细胞的胰岛)移植到无胸腺小鼠的胰腺或肾被膜下。这些胰岛移植显示,胰岛移植中形成的新血管结构中GFP阳性细胞很少,因此主要是受体来源。胰腺内移植部位血管向内生长更好的原因值得进一步研究,因为这可能有助于我们制定策略,克服宿主血管向内生长到异位移植部位胰岛中的障碍。

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1
Beneficial role of pancreatic microenvironment for angiogenesis in transplanted pancreatic islets.胰腺微环境对移植胰岛血管生成的有益作用。
Cell Transplant. 2009;18(1):23-30. doi: 10.3727/096368909788237131.
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Low revascularization of human islets when experimentally transplanted into the liver.当将人类胰岛实验性地移植到肝脏中时,其血管重建程度较低。
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Donor islet endothelial cells participate in formation of functional vessels within pancreatic islet grafts.供体胰岛内皮细胞参与胰岛移植体内功能性血管的形成。
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Impaired revascularization of transplanted mouse pancreatic islets is chronic and glucose-independent.移植小鼠胰岛的血管再生受损是慢性的且不依赖于葡萄糖。
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2
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A Metabolomic Approach (H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers.一种由组织学支持的代谢组学方法(高分辨魔角旋转核磁共振波谱法)用于研究胰岛移植肝脏的早期移植后反应。
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