Composite allo-tissue grafting by the induction of selective immunotolerance using adenovirus vectoe
Composite allo-tissue grafting by the induction of selective immunotolerance using adenovirus vectoe
批准号:
13557147
负责人:
SHIBATA Minoru
金额:
$8.9万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2001
资助国家:
日本
项目状态:
已结题
起止时间:
2001 至 2003
中文摘要
由于难以制备足够量的猴CTLA 4球蛋白,因此改变了使用选择性免疫耐受诱导的预处理。相反,采用了如用于人手移植的FK-506、MMF和泼尼松的组合使用的免疫抑制。本研究中使用了三对雌性-雄性食蟹猴。右手在前臂远端水平截肢,并在每对中交换。然后将手再植,以允许使用性别差异进行嵌合体研究。在手术过程中,组织了两个手术小组,由每个小组进行手部再植。采用钢板螺钉固定尺桡骨,再行血管吻合术,尽量缩短缺血时间。肌腱和神经在这些手术后进行了修复。在第一对中,在移植手术后口服免疫抑制剂,并在移植后进行血管吻合。 关于我们 截肢水平。由于血管尺寸较小,接受雄性猴手部的雌性猴未实现血管通畅。移植到雄猴身上的雌猴手也未能存活,尽管第一周表现良好。在第二对中,在肘部水平进行血管吻合,获得了更好的吻合,但术后没有维持口服药物。移植到雄性猴的雌性手在术后早期表现出良好的血管通畅性,但通常注意到与急性切除相关的肿胀和炎症变化。在第三对中,通过肌肉注射给予FK-506并维持足够的药物谷浓度,但由于未知原因,在手术过程中没有获得近端再灌注,并且移植的手不能存活。术后第1天,雌猴的雄手灌注成功,无明显排斥反应,随后逐渐处死,每只猴的Fax研究与术前、术后结果比较,未见明显的免疫学变化。少
英文摘要
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
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