Melzi R, Sanvito F, Mercalli A, Andralojc K, Bonifacio E, Piemonti L
Beta Cell Biology Unit, Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy.
Cell Transplant. 2008;17(12):1361-70. doi: 10.3727/096368908787648146.
Although in a clinical setting islet transplantation is normally performed by percutaneous intrahepatic infusion, the kidney capsule has been the site of choice in nearly all the studies using mice. In the present study, we extensively characterized the mouse model of intraportally transplanted islets with the purpose to propose it as a model to study islet transplantation. C57BL/6 (n = 78) and BALB/C (n = 53) recipients were transplanted with 400 autologous islets alternatively through the portal vein (PV-Tx) or under the kidney capsule (KC-Tx). Glucose concentration during the first hour after syngeneic islet infusion was associated with subsequent long-term function confirming that early events have long-term effects on graft function. In both strains tested the probability to achieve islet function was significantly lower for PV-Tx than KC-Tx. Also in allogeneic models (C57BL/6 to BALB/C, n = 104; BALB/C to C57BL/6, n = 77) the probability to achieve primary function was significantly lower for PV-Tx than KC-Tx and the site of transplantation significantly affected the graft survival. Histological evaluation of livers showed the presence of features (embolism, thrombosis, focal areas of liver necrosis) that are absent in the kidney subcapsular site. Finally, significant differences in the outcome of PV-Tx were observed between the Th type 1 inflammatory-prone C57BL/6 mouse and the type 2 inflammatory-prone BALB/C mouse. Intraportal islet graft model has some features that are more similar to human clinical islet transplantation and should be used as a model to study not only engraftment but also mechanisms of immune suppression and immune tolerance.
尽管在临床环境中胰岛移植通常通过经皮肝内输注进行，但在几乎所有使用小鼠的研究中，肾包膜一直是首选的移植部位。在本研究中，我们对门静脉内移植胰岛的小鼠模型进行了广泛的特征描述，目的是将其作为一种研究胰岛移植的模型。将C57BL/6（n = 78）和BALB/C（n = 53）受体通过门静脉（PV-Tx）或肾包膜下（KC-Tx）交替移植400个自体胰岛。同基因胰岛输注后第一小时的血糖浓度与随后的长期功能相关，证实早期事件对移植物功能有长期影响。在两种测试品系中，PV-Tx实现胰岛功能的概率均显著低于KC-Tx。在同种异体模型（C57BL/6至BALB/C，n = 104；BALB/C至C57BL/6，n = 77）中，PV-Tx实现初次功能的概率也显著低于KC-Tx，且移植部位对移植物存活有显著影响。肝脏的组织学评估显示存在肾包膜下部位所没有的特征（栓塞、血栓形成、肝坏死灶）。最后，在1型炎症易感的C57BL/6小鼠和2型炎症易感的BALB/C小鼠之间观察到PV-Tx结果的显著差异。门静脉内胰岛移植模型具有一些与人类临床胰岛移植更相似的特征，不仅应作为研究植入的模型，还应作为研究免疫抑制和免疫耐受机制的模型。
