2004 Fiscal Year Final Research Report Summary
Induction of insulin secreting cell and its application for transplantation
| Project/Area Number |
14370346
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tohoku University |
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Principal Investigator |
SUNAMURA Makoto Tohoku University, Hospital, Lecturer, 病院, 講師 (10201584)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Jyunichi Osaka University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (10200156)
HAMADA Hirofumi Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (00189614)
EGAWA Shinichi Tohoku University, Hospital, Research Associate, 病院・助手 (00270679)
FUKUYAMA Shoji Tohoku University, Hospital, Research Associate, 病院・助手 (10344673)
MATSUNO Seiki Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80004737)
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| Project Period (FY) |
2002 – 2004
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| Keywords | pancreatic ductal epithelium / insulin secreting cell / pancreatic islet regeneration / PDX-1 gene / microarray analysis |
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| Research Abstract |
Islet transplantation has been expected to be effective therapy for insulin dependent DM (IDDM). However, this strategy is not established as a standard treatment for IDDM yet. The control of immuno-rejection is an obstacle for islet transplantation as same as the shortage of donors. The aim of this study is to develop the islet transplantation by using regeneration islet.
1.The induction of insulin secreting cells from human pancreatic duct cell (HPDC)
1)We established the HPDC cell line by the transfection of early expression gene of papilloma virus.
2)The change of shape of this HPDC was observed after the stimulation of extra cellular matrix of tissue culture.
3)We constructed the adenovirus vector for the transfection of PDX-1 gene. After transfection of PDX-1 gene into HPDC, the more expression of glucagon was detected than that of insulin. The cells made a mass looking like islet after in vitro culture. These HPDC became neoplastic tumor in vivo transplantation in mice.
2.The analysis of genes expression using microarray and the detection of genes relating to islet development
1)The mRNA was extracted from HPDC showing the insulin expression and used for DNA microarray study. The exspression of insulin was detected and genes showing the same pattern as insulin were selected.
2)The collaborate group has established insulin secreting cell from mouse embryonic stem cell (ISSC). We harvested the cells from 5 stage of this development and analyzed the mRNA expression using microarray system. The analysis of changes in gene expression revealed that the expression of genes relating to insulin was increased step by step. Theses results indicate that the responsible gene would be detected by the further study.
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