Project/Area Number |
17591335
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
|
Research Institution | HIROSHIMA UNIVERSITY |
Principal Investigator |
UEMURA Kenichiro Hiroshima University, Hospital, Research Associate, 病院, 助手 (60379873)
|
Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Yoshiaki Hiroshima University, Hospital, Assistant Professor, 病院・講師 (10263683)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
Keywords | hepatic regeneration / islet transplantation / promoting effect on engraftment / growth factor / micro array |
Research Abstract |
PURPOSE : To achieve successful insulin independence after single-donor islet transplantation, we had examined the impact of hepatic regeneration on engraftment of islet cells transplanted intraportally in the immediate postoperative period. We demonstrated that hepatic regeneration promotes functional engraftment and ameliorates insulin secretion and posttransplantation hyperglycemia in rat. The aim of this study was to clarify promoting effect on engraftment of intraportally transplanted islet cells under hepatic regeneration by exhaustive gene analysis using micro array. METHODS : Isolated pancreatic islets from a single-donor were intraportally transplanted to streptozotocin-diabetic rats immediately after 70% partial hepatectomy (HxPIT) and were also transplanted to the rats without hapatectomy (PIT). The livers were removed from the recipient rats after 24 hours posttransplantation, and then RNA was extracted from intrahepatic engrafted islet cells. We analyzed gene expression of the RNA using rat micro array (Rat Genome 230 2.0 Array). RESULTS : Morphologically, grafted islets from HxPIT rats were large and granulated by hypertrophic beta cells. The sizes of the grafted islets and indivisual insulin-stained islet cells were larger than those from PIT rats. The gene analysis using micro array demonstrated that the expression of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) of the RNA extracted from HxPIT rats was statistically higher than that from PIT rats. FUTURE EVOLUTION : For the future, we will extract RNA from grafted islets using microdissection technique to exclude most surely the RNA without grafted islet cells. And then, we will use green rats (green fluorescent protein ; GFP gene transfer rats) for the donor in islet transplantation to extirpation selectively only islet cells using microdissection technique under the fluorescent microscope.
|