Project/Area Number |
13557147
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Plastic surgery
|
Research Institution | NIIGATA UNIVERSITY |
Principal Investigator |
SHIBATA Minoru NIIGATA UNIVERSITY, Medical & Dental Hospital, Professor, 医歯学総合病院, 教授 (50196432)
|
Co-Investigator(Kenkyū-buntansha) |
SAKAMURA Ritsuo Plastic Surgery, Medical & Dental Hospital, Assistant, 医歯学総合病院, 助手 (90322106)
ENDO Naoto NIIGATA UNIVERSITY, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (10251810)
UEDE Toshimitu Hokkaido University, Institute for Genetic Medicine, Professor, 遺伝子病制御研究所, 教授 (00160185)
|
Project Period (FY) |
2001 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
|
Keywords | Monkey / Hand allo-grafting / immunosuppression / 同種手移植 / CD3 immunotoxin |
Research Abstract |
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
|