Department of Surgery, Columbia University Medical College, New York, NY, USA.
Transplantation. 2009 Nov 15;88(9):1065-74. doi: 10.1097/TP.0b013e3181ba2e87.
Because the hepatic portal system may not be the optimal site for islet transplantation, several extrahepatic sites have been studied. Here, we examine an intramuscular transplantation site, bioengineered to better support islet neovascularization, engraftment, and survival, and we demonstrate that at this novel site, grafted beta cell mass may be quantitated in a real-time noninvasive manner by positron emission tomography (PET) imaging.
Streptozotocin-induced rats were pretreated intramuscularly with a biocompatible angiogenic scaffold received syngeneic islet transplants 2 weeks later. The recipients were monitored serially by blood glucose and glucose tolerance measurements and by PET imaging of the transplant site with [11C] dihydrotetrabenazine. Parallel histopathologic evaluation of the grafts was performed using insulin staining and evaluation of microvasularity.
Reversal of hyperglycemia by islet transplantation was most successful in recipients pretreated with bioscaffolds containing angiogenic factors when compared with those who received no bioscaffolds or bioscaffolds not treated with angiogenic factors. PET imaging with [11C] dihydrotetrabenazine, insulin staining, and microvascular density patterns were consistent with islet survival, increased levels of angiogenesis, and with reversal of hyperglycemia.
Induction of increased neovascularization at an intramuscular site significantly improves islet transplant engraftment and survival compared with controls. The use of a nonhepatic transplant site may avoid intrahepatic complications and permit the use of PET imaging to measure and follow transplanted beta cell mass in real time. These findings have important implications for effective islet implantation outside of the liver and offer promising possibilities for improving islet survival, monitoring, and even prevention of islet loss.
由于肝门静脉系统可能不是胰岛移植的最佳部位，因此已经研究了几个肝外部位。在这里，我们研究了一种肌肉内移植部位，该部位经过生物工程改造，可更好地支持胰岛新生血管形成、植入和存活，并且我们证明，在这个新部位，可以通过正电子发射断层扫描（PET）成像实时、非侵入性地定量移植的β细胞质量。
链脲佐菌素诱导的大鼠经肌肉内预先用生物相容性血管生成支架处理，2 周后接受同种异体胰岛移植。通过血糖和葡萄糖耐量测量以及通过 [11C] 二氢四苯并嗪对移植部位的 PET 成像，对受者进行连续监测。使用胰岛素染色和微血管评估平行进行移植组织的组织病理学评估。
与未接受生物支架或未用血管生成因子处理的生物支架的受者相比，用含有血管生成因子的生物支架预处理的受者接受胰岛移植后，逆转高血糖的效果最为成功。[11C]二氢四苯并嗪的 PET 成像、胰岛素染色和微血管密度模式与胰岛存活、新生血管增加水平以及高血糖逆转一致。
与对照相比，在肌肉内部位诱导增加新生血管形成可显著改善胰岛移植的植入和存活。使用非肝移植部位可避免肝内并发症，并允许使用 PET 成像实时测量和跟踪移植的β细胞质量。这些发现对于在肝脏外进行有效的胰岛植入具有重要意义，并为提高胰岛存活、监测甚至预防胰岛丢失提供了有希望的可能性。
