Microchimerism and Transplantation Tolerance
| Project/Area Number |
08671534
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Miyazaki Medical College |
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Principal Investigator |
ONITSUKA Toshio Miyazaki Medical College, Faculty of Medicine, Professor, 医学部, 教授 (60108595)
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| Co-Investigator(Kenkyū-buntansha) |
SEKIYA Ryou Miyazaki Medical College, Faculty of Medicine, Research Associate, 医学部, 助手 (00206640)
MATSUZAKI Yasunori Miyazaki Medical College, Faculty of Medicine, Associate Proffesor, 医学部, 助教授 (90190446)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | microchimerism / heart transplantation / rat / origin / skin transplantation / tolerance / microchimerism, / heart transplantation, / rat, |
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| Research Abstract |
Introduction : To address the relationship between microchimerism and the maintenance of tolerance the following experimental groups were set up.
Methods : Group 1 : Chimeric hearts from female LEW.1A rats which had been irradiated (15Gy) and reconstituted with bone marrow from male LEW.1A rats were transplanted into nave unirradiated female LEW.1A rats. All hearts continued to function. Sixty days after transplantation, recipients had the transplanted hearts explanted. Four months later the same animals were sensitised with 1 x 105 dendritic cells (DC) from male LEW.1A rats, and 14 days later transplanted with skin from male rats of the same strain. Group 2 : Control nave female LEW.1A rats were sensitised with 1 x 105 DC from male LEW.IA rats and 14 days later were transplanted with male LEW.1A skin grafts. Peripheral blood michrochimerism (PBMC) was evaluated by PCR every two weeks employing primers specific for the sex determining Y-chromosome. .
Results : In Group 1, PBMC was detect
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ed 60 days following heart transplantation in eight of nine rats. Following removal of hearts, PBMC was gradually lost in the majority of rats. However, two of nine rats showed PBMC at four months. All Group 1 female rats (n=9) were sensitised with DC (subcutaneously) and transplanted with skin from nave male LEW.IA rats. Seven of nine recipients rejected the male skin grafts within 15 days. Interestingly, the two recipients who had not rejected male skin acutely were those that had stable PBMC at the time of DC sensitisation. These two recipients were unable to reject (MST> 100 days) in spite of being sensitised in an identical fashion. All control animals in Group 2 (n=6) rejected male skin grafts acutely within 12 days.
Conclusion : Microchimerism detected in peripheral blood can be maintained for long periods of time (4 months). Microchimeric cells are bone marrow derived cells. The ability to detect microchimeric cells is associated with the maintenance of tolerance to skin grafts across an H-Y minor histocompatibilty barrier. Less
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Report
(4 results)
Research Products
(4 results)
