Carlsson Per-Ola, Palm Fredrik, Mattsson Göran
Department of Medical Cell Biology, Uppsala University, SE-751 23 Uppsala, Sweden.
J Clin Endocrinol Metab. 2002 Dec;87(12):5418-23. doi: 10.1210/jc.2002-020728.
Pancreatic islets are avascular immediately after transplantation. Although the islets are rapidly revascularized, it is uncertain whether the revascularization produces an adequate oxygenation of the transplanted islet tissue. We measured pO(2), blood flow and vascular density in mouse or human islets 1 month after transplantation to nude mice. Tissue pO(2) was measured with Clark microelectrodes. Blood perfusion was measured with laser-Doppler flow cytometry, whereas vascular density was determined in histological specimens stained for the lectin Bandeiraea simplicifolia (BS-1). Both the transplanted mouse and human islets had a pO(2) 15-20% of that in endogenous mouse islets. Moreover, the vascular density of the transplanted islets was decreased compared with that of endogenous mouse and human islets. Graft blood perfusion was approximately 50% of renal cortex blood flow. A negative correlation was found between donor age and blood perfusion of the human islet grafts. A similar correlation was seen between donor age and the total vascular density of these grafts. In conclusion, transplanted human islets had a markedly decreased vascular density and pO(2) compared with endogenous islets. This has potential implications for clinical islet transplantations, because poor vascular engraftment may significantly increase the number of islets needed to obtain insulin independence.
移植后即刻,胰岛是无血管的。尽管胰岛会迅速重新血管化,但重新血管化是否能为移植的胰岛组织提供充足的氧合尚不确定。我们测量了移植到裸鼠体内1个月后的小鼠或人胰岛的pO₂、血流和血管密度。用Clark微电极测量组织pO₂。用激光多普勒流式细胞术测量血流灌注,而血管密度则在经单叶豆凝集素(BS-1)染色的组织学标本中测定。移植的小鼠和人胰岛的pO₂均为内源性小鼠胰岛的15%-20%。此外,与内源性小鼠和人胰岛相比,移植胰岛的血管密度降低。移植物的血流灌注约为肾皮质血流的50%。在供体年龄与人胰岛移植物的血流灌注之间发现了负相关。在供体年龄与这些移植物的总血管密度之间也观察到类似的相关性。总之,与内源性胰岛相比,移植的人胰岛的血管密度和pO₂明显降低。这对临床胰岛移植具有潜在影响,因为血管植入不良可能会显著增加实现胰岛素自主所需的胰岛数量。