Mattsson Göran
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Ups J Med Sci. 2005;110(1):1-15. doi: 10.3109/2000-1967-081.
The blood vessels of the pancreatic islets are of crucial importance for oxygen and metabolite supply, and dispersal of secreted hormones. In addition to this, endothelial cells have an important role in the revascularization process after islet transplantation. Studies have reported signs of poor engraftment of transplanted islets, presumably due to impaired revascularization. The aims of this study were to investigate islet endothelial cells and the revascularization process of transplanted islets. The lectin Bandeiraea simplicifolia was found to consistently stain endothelium of both endogenous and transplanted pancreatic islets. By using this marker, we investigated the vascular density of both endogenous and transplanted islets of C57BL/6 mice. One month post-transplantation, a time point when the implants are assumed to be completely revascularized, the graft vascular density was decreased at all investigated implantation sites when compared to endogenous islets. Furthermore, most of the blood vessels were located in the graft connective tissue stroma. Similar results were obtained six months post-transplantation and in cured diabetic animals after one month. In order to evaluate the function of intraportally transplanted islets, we developed a method to retrieve such islets. Enzymatic and mechanic treatment of the liver enabled us to re-isolate the transplanted islets for further in vitro studies. These islets had decreased insulin release, insulin content and glucose oxidation rate when compared to non-transplanted control islets. To understand the role of islet endothelium in the revascularization of transplanted islets we performed angiogenesis microarray studies on islet endothelial cells, from non-cultured, cultured and transplanted islets. We found that the islet endothelium expressed mRNA for both inhibitors and inducers of angiogenesis, and that this expression differed with time. In conclusion, these results provide a useful platform for further studies on the islet endothelium.
胰岛的血管对于氧气和代谢物的供应以及分泌激素的扩散至关重要。除此之外，内皮细胞在胰岛移植后的血管再生过程中发挥着重要作用。研究报道了移植胰岛植入不佳的迹象，推测是由于血管再生受损所致。本研究的目的是调查胰岛内皮细胞和移植胰岛的血管再生过程。发现凝集素单叶豆一直能对内源性和移植的胰岛内皮进行染色。通过使用该标记物，我们研究了C57BL/6小鼠内源性和移植胰岛的血管密度。移植后一个月，这是假定植入物已完全血管化的时间点，与内源性胰岛相比，在所有研究的植入部位，移植胰岛的血管密度均降低。此外，大多数血管位于移植胰岛的结缔组织基质中。在移植后六个月以及治愈的糖尿病动物在一个月后也获得了类似的结果。为了评估门静脉内移植胰岛的功能，我们开发了一种回收此类胰岛的方法。对肝脏进行酶促和机械处理使我们能够重新分离移植的胰岛以进行进一步的体外研究。与未移植的对照胰岛相比，这些胰岛的胰岛素释放、胰岛素含量和葡萄糖氧化率均降低。为了了解胰岛内皮在移植胰岛血管再生中的作用，我们对来自未培养、培养和移植胰岛的胰岛内皮细胞进行了血管生成微阵列研究。我们发现胰岛内皮表达血管生成抑制剂和诱导剂的mRNA，并且这种表达随时间而不同。总之，这些结果为进一步研究胰岛内皮提供了一个有用的平台。
