Project/Area Number |
11470256
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | The University of Tokyo |
Principal Investigator |
SUGAWARA Yasuhiko (2000-2001) The University of Tokyo, Artificial Orgam & Transplant at surgery, Associate Professor, 医学部・附属病院, 助教授 (90313155)
針原 康 (1999) 東京大学, 医学部・付属病院, 講師 (10189714)
|
Co-Investigator(Kenkyū-buntansha) |
IWAMURA Hiroshi The University of Tokyo, Artificial Orgam & Transplant at surgery, Lecturer, 医学部・附属病院, 講師 (00283268)
菅原 寧彦 東京大学, 医学部・附属病院, 助手 (90313155)
|
Project Period (FY) |
1999 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2001: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2000: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1999: ¥3,600,000 (Direct Cost: ¥3,600,000)
|
Keywords | xenotranplantation / Cardiac transplantation / Liver Transplantation / Concordant / Discordant |
Research Abstract |
Background : Delayed xenograft rejection (DXR) is the main obstacle in discordant xenotranplantation. Using a mouse-to-rat concordant cardiac transplantation model and DNA microarray, we study the gene expression profile during acute rejection. Material and Methods : Inbred BALB/c and C3H/He mice (male, 6- 8 weeks) and Lewis rats (male, 8-14 days) were purchased. Heterotopic cardiac transplantaitons were performed. Total RNA was isolated from xenograft (mouse to rat), allpgraft (BALB/c mouse to C3H mouse), rat Isograft (rat to rat)and mouse isograft (C3H to C3H) on day 5 respectively. We screened for gene- expression profile in xenograft, allograft and mouse isograft by means of Affymetrix mousellK arrays. Xenograft and rat isograft were also analyzed bymeans of Affymetrix rat U74A arrays. Results: In mouse to rat cardiac xenografts and murine allografts, complete rejection occurs 7.0±0.7 days and 8.0 ±0.6 days. Cardiac isografts in both rat and mouse recipients function for more than 100 days. By means of murine array, many IFN gammma inducible genes were profoundly expressed in the both allograft and xenograft relative to isograft; MRP-8, MRP14 and MAC induced relative to allograft. Using a rat array, cardionatrln and ANF were most profoundly expressed in the xenograft in comparison with the rat Isograft. In addition to known genes, many ESTs were induced in xenograft. Conclusions: Thesegenes were considered to be involved DXR and new therapeutic target of DXR.
|