Composite allo-tissue grafting by the induction of selective immunotolerance using adenovirus vectoe

由于难以制备足量的猴用CTLA4球蛋白，改变了选择性免疫耐受诱导的预处理方法。相反，采用了手移植中使用的FK-506、MMF和强的松联合使用的免疫抑制方法。本研究使用了三对雌性-雄性食蟹猴。在前臂远端截去右手，每对互换。然后移植双手，利用性别差异进行嵌合研究。术中组织两个手术小组，各小组分别进行手部再植。采用钢板、螺钉固定尺骨、桡骨后进行血管吻合，缩短缺血时间。肌腱和神经在手术后得到修复。第一对在移植手术后口服免疫抑制药物，在断肢水平进行血管吻合。接受雄猴手的雌猴由于血管小，没有达到血管通畅。移植到雄猴身上的雌手也没能存活，尽管它在第一周存活得很好。第二对在肘关节处进行血管吻合，吻合效果较好，但术后未维持口服药物。移植到雄猴身上的雌性手在术后早期表现出良好的血管通畅，然而急性切除后出现了典型的肿胀和炎症变化。在第三对中，FK-506通过肌肉注射给药，维持了足够的药槽水平，但由于未知的原因，手术中没有达到近端再灌注，移植手无法存活。雌猴的雄手在术后第1天灌注成功，未出现强烈的排斥反应，随后移植的手逐渐被杀死。在每只猴子的Fax研究中，与术前和术后的结果相比，没有显示出显著的免疫变化。少

Preconditioning using selective immuno-tolerance induction was changed because of the difficulty to prepare sufficient amount of CTLA4 globulin for monkey. Instead, immunosuppression by the combination use of the FK-506, MMF and Prednisone as is used for human hand transplantation was adopted. Three female-male pairs of cynomolgus-monkeys were used in this study. The right hands were amputated at distal forearm level and exchanged in each pair. Then the hands were replanted to allow chimerism study using sex difference. During the surgery, two surgical teams were organized and conducted replantation of the hand by the each team. Plate and screws were used for the fixation of ulna and radius bones and then the vascular anastomosis was carried out to minimize the ischemic time. Tendons and nerves were then repaired after those procedures. In the first pair, the immunosuppression drugs were given orally after the surgery for transplantation, and vascular anastomosis was carried out at the … More amputated level. The vascular patency was not achieved in the female monkey which received male monkey's hand because of small sized vessels. The female hand grafted to the male monkey also failed to survive, although it did well in the first week.In the second pair, the vascular anastomosis was carried out at elbow level and better anastomosis was attained, but the oral medication was not maintained postoperatively. The female hand grafted to the male monkey demonstrated good vascular patency in the early postoperative days, however swelling and inflammatory change associated with acute resection was typically noted.In the third pair, the FK-506 was administrated through intramuscular injection and sufficient drug trough level was maintained, However, because of unknown reasons, proximal reperfusion was not attained during surgery and the grafted hand was not able to survive. The male hand on the female monkey demonstrated successful perfusion without showing strong rejection signs during the first postoperative the days, and then transplanted hand was gradually killed.Fax study in each monkey did not show remarkable immunological change comparing preoperative and postoperative results. Less