2005 Fiscal Year Final Research Report Summary
EXPERIMENTAL ANALYSIS OF VASCULER CHANGES IN CHRONIC ALLOGRAFT REJECTION USING HUMANIZED SCID MOUSE MODEL.
| Project/Area Number |
14571526
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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 |
Urology
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| Research Institution | FUJITA HEALTH UNIVERSITY |
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Principal Investigator |
SHIROKI Ryoichi FUJITA HEALTH UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (70226330)
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| Co-Investigator(Kenkyū-buntansha) |
HOSHINAGA Kiyotaka FUJITA HEALTH UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (30229174)
SASAKI Hitomi FUJITA HEALTH UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (00319261)
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| Project Period (FY) |
2002 – 2005
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| Keywords | organ transplantation / chronic rejection / SCID mouse |
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| Research Abstract |
Chronic allograft nephropathy (CAN) is the most common cause to graft failure in clinical kidney transplantation. The appropriate therapeutic strategies to CAN, however, is yet to be established because of the various etiology and rationale of CAN. Basic pathophysiology of CAN is accounted for vascular inflammation leading to fibrosis and screlosis. Our study goal was to analyze and characterize CAN in animal model using hu-PBL-SCOD mouse. Humanized severe combined immunodeficient (SCID) mice, which exhibited human immunological environment, were established by administration of human peripheral blood lymphocytes (PBL). These huPBL-SCID mice were also demonstrated to involve functional human lymphocyte and immunoglobulin in their circulation. To display the real CAN of human allotransplant circumstances in mouse, human mesenteric arterior was applied for direct bypass of abdominal aorta in hu-PBL-SCID. Analysis of recovered vascular graft revealed lymphocytes invasion on the endothelium of the vascular graft. Pathological analysis indicated these graft-infiltrating-lymphocytes (GIL) belonged to CD3+CD4+ in staining. Next, we tried to determine the optimal time to see the cellular rejection by changing the recovering time of graft. Stable model of the cellular rejection were, however, difficult to establish due to the inter-individual differences. We also tried to establish the GIL cell line in vitro by recovering these grafts to tissue culture. This experiment, however, resulted in discontinued because of the contaminations and slow growing GILs. Messenger RNA expression of TNF-alpha and IFN-gamma were noted in recovered human mesenteric arterior using PCR analysis applying the appropriate anti-sense oligonucleotides. On the other hand, no particular messenger expression of adhesion molecules associated with cell migration or chemokines in our experimental condition.
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