| Project/Area Number |
10307029
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
AGISHI Tetsuzo Tokyo Women's Medical University Surgery III, Professor, 医学部, 教授 (70090660)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Yuichi Tokyo Women's Medical University Surgery III, Assistant, 医学部, 助手 (80231348)
KIMIKAWA Masaaki Tokyo Women's Medical University Surgery III, Assistant, 医学部, 助手 (70204964)
TERAOKA Satoshi Tokyo Women's Medical University Surgery III, Professor, 医学部, 教授 (20147383)
ISHII Yasuo Tokyo Women's Medical University Surgery III, Assistant, 医学部, 助手 (80318039)
HIROTANI Sachiko Tokyo Women's Medical University Surgery III, Assistant, 医学部, 助手 (70211513)
中村 道郎 東京女子医科大学, 医学部, 助手 (00246547)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥36,300,000 (Direct Cost: ¥36,300,000)
Fiscal Year 1999: ¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 1998: ¥21,100,000 (Direct Cost: ¥21,100,000)
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| Keywords | transplantation / tolerance / apoptosis in lymphocytes / kidney transplantation / bone marrow transplantation / peripheral blood stem cel transplantation |
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| Research Abstract |
In 1998 and the first half of 1999, studies were designed to induce transplantation tolerance by means of drug-induced apoptosis in lymphocytes. In these studies, kidney transplantaions were performed with donor bone marrow infusion and preoperative administration of Busulfan and FTY.
In the first two cases, Busulfan was administered at a dosage of 4 mg/kg/day from day -7 to day -4 and FTY was administered at a dosage of 5mg/kg/day from day -2 to day 0. Unfortunately, severe pancytopenia appeared in both cases and one monkey died of sepsis. Although Busulfan was reduced to 3 mg/kg/day in the next three monkeys, mixed chimerism did not develop and the transplant kidneys were rejected in all cases.
In the latter half of 1999, the studies were modified as follows. (1) Replacing Busulfan, Cyclophosphamide was administered for the purpose of myelosuppression and immunosuppression. (2)The previous method, in which bone marrow was obtained from the donor's iliac crest and/or vertebral bone by multiple aspirations, was changed. To obtain large numbers of monkey hematopoietic cells, leukapheresis was used to collect blood cell products in monkeys after progenitor cell mobilization by using human granulocyte colon-stimulating factor (G-CSF). As a result, a large number of hematopoitic cells were collected and infused. By this new potocol, two monkeys have survived with normal kidney function for more than three months without administration of any immunosuppression.
In future, donor-specific unresponsiveness will be confirmed by using mixed lymphocyte reaction (MLR) and donor-specific tolerance will be confirmed by using skin grafting.
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