2001 Fiscal Year Final Research Report Summary
ESTABLISHMENT OF IMMUNOSUPPRESIVE METHOD FOR CLINICAL DISCORDANT XENOGENEIC CARDIAC TRANSPLANTATION
| Project/Area Number |
11470272
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
OHTAKE Shigeaki Osaka Univ. Graduate School of Med Lecturer, 医学系研究科, 講師 (50243209)
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| Co-Investigator(Kenkyū-buntansha) |
SAWA Yoshiki Osaka Univ. Graduate School of Med Lecturer, 医学系研究科, 講師 (00243220)
FUKUSHIMA Norihide Osaka Univ. Graduate School of Med Assistant Professor, 医学系研究科, 助手 (30263247)
SHIRAKURA Ryota Osaka Univ. Graduate School of Med Professor, 医学系研究科, 教授 (00116047)
SAKAKIDA Satoru Osaka Univ. Graduate School of Med Associate Professor, 医学系研究科, 助教授 (90311753)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Xenotransplantation / Babboon / Pig / Anti-pig antibody / Hyperacute rejection / CAM / FK506 |
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| Research Abstract |
A. Immunological Assessment of Baboon and Pigs
1) Establishment of assay of anti-pig antibody (against red blood cells by titration method and against endothelial cells or leukocytes by ELISA)
2) Mixed lymphocyte culture (MLC) of baboon lymphocytes against pig lymphocytes
3) Assay of subpopulation of baboon lymphocytes using anti-human lymphocytes
B. Prolonged xenograft survival by sequential heterotopic heart transplantation in pig-to-baboon model.
It has been well known that natural antibodies played a major role in hyperacute rejection (HAR) in a pig-to-baboon cardiac xenograft model. In the present study, baboons were transplanted three to four pig hearts sequentially to determine how many sequentially transplant hearts are necessary to absorb anti-pig antibody (Ab) to the level that may not cause HAR in the last transplanted heart. Materials and Methods 4 baboons received FK506 and CAM in oral doses of 12 mg/Kg and 50 mg/Kg for 2 weeks before transplantation (HTx). Each baboon underwen
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t three to four sequential heterotopic HTx from pigs of the almost same size as the recipient baboon in the right neck. Grafts except the last one were removed soon after rejected or 2 hours after HTx if not rejected. Blood was sampled from the femoral artery (FA) of the recipient and the coronary sinus (CS) of the graft to measure anti-pig red-blood-cell Ab. Results All first graft was hyperacutely rejected within 30 minutes after HTx. 2 second grafts was rejected within 2 hours after HTx. 2 second and all third grafts were not rejected within 2 hours after HTx. One graft survived one day after HTx and arrested because of rejection. Another graft survived for 6 days after HTx, while the other two baboons died of hypotension after the last graft was transplanted. In each point, Ab in the baboon FA was higher than that in the graft CS. Ab in the baboon FA decreased gradually after sequential HTx and finally became undetected before the last graft was transplanted. All first grafts showed histologically massive hemorrhage and myocyte necrosis which suggested HAR, while the second and third grafts showed only some kind of ischemic changes with myocyte necrosis. Conclusion These data suggested that absorption of baboon anti-pig antibody using more than two hearts of the same size as the recipient baboon may reduce anti-pig Ab to the level that did not cause HAR in the subsequent graft. Less
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