Bartlett S T, Hadley G A, Dirden B, Schweitzer E J, Eans S, Pham D, Sheffield C
Department of Surgery, University of Maryland Medical Systems, Baltimore 21201.
Surgery. 1993 Aug;114(2):211-7.
Clinically successful islet transplantation has been rare despite adequate isolation techniques. Reenactment of the original autoimmune beta-cell destruction may contribute to the poor results. Distinguishing autoimmune effects from rejection can be accomplished with isogeneic transplants exchanged between diabetes-prone (BB-DP) and diabetes-resistant (BB-DR) rats. These experiments determine the relative sensitivity of islet, whole pancreas, and composite kidney-islet transplants to recurrent autoimmunity.
Acutely diabetic (BB-Ac) BB rats served as recipients of vascularized pancreas, intraportal (IPo) or renal capsular (KC) islet transplants, or vascularized composite kidney-islet grafts from BB-DR or BB-DP donors. Graft function was assessed by daily blood glucose level, and the outcome was confirmed on histologic examination. Cyclosporine 5 mg/kg/day intramuscularly was administered to assess its effect on recurrent beta-cell injury.
BB-DP pancreases developed recurrent autoimmunity in 55% of cases; cyclosporine afforded complete protection if maintained. Diabetes resistance was transplanted with 23 of 23 BB-DR pancreas grafts; however, islet isolation led to a loss of diabetes resistance for islet grafts to the KC and IPo. Cyclosporine protected KC but not IPo islets. Composite BB-DR kidney-islet transplants functioned indefinitely in all cases.
Transplanted islets initially survive by passive diffusion but are ultimately revascularized by capillary ingrowth. The finding that composite kidney-islet transplants function indefinitely suggests that the revascularizing endothelium may play a role in resistance or susceptibility to autoimmune beta-cell destruction.
尽管有足够的分离技术，但临床上成功的胰岛移植仍然很少见。原始自身免疫性β细胞破坏的重演可能导致不良结果。通过在易患糖尿病（BB-DP）和抗糖尿病（BB-DR）大鼠之间交换同基因移植，可以区分自身免疫效应和排斥反应。这些实验确定了胰岛、全胰腺和复合肾-胰岛移植对复发性自身免疫的相对敏感性。
急性糖尿病（BB-Ac）BB大鼠作为接受者，接受来自BB-DR或BB-DP供体的血管化胰腺、门静脉内（IPo）或肾包膜下（KC）胰岛移植，或血管化复合肾-胰岛移植物。通过每日血糖水平评估移植物功能，并通过组织学检查确认结果。给予环孢素5mg/kg/天肌肉注射，以评估其对复发性β细胞损伤的影响。
BB-DP胰腺在55%的病例中出现复发性自身免疫；如果持续使用，环孢素可提供完全保护。23例BB-DR胰腺移植物中有23例移植后具有抗糖尿病能力；然而，胰岛分离导致移植到KC和IPo的胰岛失去抗糖尿病能力。环孢素保护KC胰岛，但不保护IPo胰岛。所有病例中，复合BB-DR肾-胰岛移植均能无限期发挥功能。
移植的胰岛最初通过被动扩散存活，但最终通过毛细血管长入实现血管化。复合肾-胰岛移植能无限期发挥功能这一发现表明，血管化内皮可能在抵抗或易患自身免疫性β细胞破坏中起作用。
