Grtochowiecki T, Gotoh M, Dono K, Takeda Y, Nishihara M, Ohta Y, Ota H, Ohzato H, Okuyama M, Shimizu J, Kimura F, He L, Nagano H, Nakamori S, Umeshita K, Sakon M, Monden M
Department of Surgery II, Osaka University Medical School, Osaka University, Japan.
Transplantation. 1999 Jun 15;67(11):1474-7. doi: 10.1097/00007890-199906150-00014.
Rejection of pancreatic islet grafts is still a serious problem. We evaluated the effect of mitomycin C (MMC) on the survival of crude islets grafts after xenogeneic islet transplantation.
WS (RT1k) rat islets pretreated with various concentrations of MMC (0, 1, 3.2, 10, 32, 50, 100, 320, and 1,000 microg/ml) were transplanted into C57BL/6 mice with streptozotocin-induced diabetes. In vivo graft function was assessed by a daily measurement of nonfasting blood glucose concentration in each animal. We also examined the separate effect of MMC on purified islets and contaminants present in the crude islet preparation.
MMC at doses of 10, 32, 50, and 100 microg/ml resulted in a significant prolongation of the mean graft survival time from a control of 12.4+/-2.5 days to 23+/-7.4, 17.5+/-5.4, 25.5+/-14.7, and 26.7+/-8.9 days, respectively. Deterioration of glucose metabolism was noted when the dose exceeded 32 microg/ml, whereas at 320 microg/ ml, MMC failed to restore normoglycemia. Prolongation of survival time of crude islets was the result of its effect on islets and contaminant components of the crude islet preparation. In vitro study showed that MMC treatment at a higher concentration than 10 microg/ml reduces the stimulatory as well as proliferative capacity of lymph node cells.
Pretreatment of pancreatic islets with MMC at 10 microg/ml prolongs xenograft survival without deterioration of in vivo graft function. This novel treatment modality represents a new strategy for the modulation of immunity of islets and contaminants in crude islet preparations.
胰岛移植排斥仍是一个严重问题。我们评估了丝裂霉素C(MMC)对异种胰岛移植后粗制胰岛移植物存活的影响。
用不同浓度MMC(0、1、3.2、10、32、50、100、320和1000微克/毫升)预处理的WS(RT1k)大鼠胰岛被移植到链脲佐菌素诱导糖尿病的C57BL/6小鼠体内。通过每天测量每只动物的非空腹血糖浓度来评估体内移植物功能。我们还研究了MMC对纯化胰岛和粗制胰岛制剂中污染物的单独作用。
剂量为10、32、50和100微克/毫升的MMC使平均移植物存活时间显著延长,从对照组的12.4±2.5天分别延长至23±7.4天、17.5±5.4天、25.5±14.7天和26.7±8.9天。当剂量超过32微克/毫升时,葡萄糖代谢出现恶化,而在320微克/毫升时,MMC未能恢复正常血糖。粗制胰岛存活时间的延长是其对胰岛和粗制胰岛制剂污染物成分作用的结果。体外研究表明,浓度高于10微克/毫升的MMC处理会降低淋巴结细胞的刺激和增殖能力。
用10微克/毫升的MMC预处理胰岛可延长异种移植物存活时间,且不会使体内移植物功能恶化。这种新的治疗方式代表了一种调节粗制胰岛制剂中胰岛和污染物免疫的新策略。