| Project/Area Number |
12670219
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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 |
Experimental pathology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
INABA Muneo Kansai Medical University Faculty of Medicine Associate Professor, 医学部, 助教授 (70115947)
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| Co-Investigator(Kenkyū-buntansha) |
HISHA Hiroko Kansai Medical University Faculty of Medicine Assistant Professor, 医学部, 講師 (90141522)
比舎 弘子 関西医科大学, 医学部, 講師 (90151422)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Bone marrow transplantation / Portal vein / donor-derived cell / hemopoietic progenitor cells / stromal cells |
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| Research Abstract |
A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in MRL/lpr mice without using immunosuppressants has been established. The method consists of fractionated irradiation (5.5 Gy x 2) followed by the portal venous (PV) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV) injection of whole B6 BMCs 5 days after the PV injection. Al recipients survived more than 1 year after this treatment. Abnormal T cells (B220+/Thy1.2+/CD3+/CD4-/CD8-) present in untreated MRL/lpr mice disappeared. In the mice thus treated, the number of donor-derived cells possessing the mature lineage (Lin) markers rapidly increased in the bone marrow, spleen, and liver, indicating that hematolymphoid cells are completely reconstituted with donor-derived cells. The number of donor-derived hemopoietic progenitor cells (c-kit+Lin- cells) increased in the BMCs, hepatic mononuclear cells, and spleen cells. Simultaneously, homopoietic foci adjoining donor-derived stromal cells were observed in the liver when injected via PV, but not IV. Furthermore, donor-derived stromal cells were detected in the BMCs after the culture. This indicates that the donor-derived stromal cells are not only trapped in the liver but also migrate into the bone marrow where they construct the hemopoietic environment.
These findings suggest that not only donor hemopoietic stem cells (HSCs) but also donor stromal cells administered via the PV were trapped in the liver, resulting in the early engraftment of donor HSCs in cooperation with donor-derived stromal cells.
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