lderitification and analysis of the factors related to the proliferation and differentiation of the adult liver progeritor cells
| Project/Area Number |
17390362
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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 |
Digestive surgery
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| Research Institution | Shinshu University |
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Principal Investigator |
MIWA Shiro Shinshu University, Departoment of Strgery, Assistant Professor (20293516)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAGAWA Shinichi Shinshu University, Departomert of Sugery, Professor (80229806)
NAKATA Takenari Shinshu Univeisity, Departomert of Surgery, 助教 (70377638)
SOEDA Junpei Shinshu Univeisity, Departomert of Surgery, 助教 (40419370)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,920,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥11,200,000 (Direct Cost: ¥11,200,000)
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| Keywords | stem cell therapy / progenitor cell / microenvironment / bone marrow cell / oval cell / hepatocarcinocienesis / 癌幹細胞 / 肝発癌 / 細胞融合 / 肝幹細胞 |
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| Research Abstract |
Infra present study, we analyzed the factors related to the proliferation and differentiation of the Inter progenitor cells.
We obtained the following new findings.
1) Ductular reaction (DR) in the liver are thought to be result from progenitor cell proliferation. We analyzed the DR in submassive hepatic necrosis (SHN) in human livers. Cells in DR expressed high level of c-met, NCAM, β-1, α 6 integrin, These cells also specifically expressed CD133 and DLK. DR always resided in a laminin rich matrix and closely contacted with o SMA positive cells. The area in which the cell differentiated toward hepatocytes contained high level of TGF a and TGF β 1 and the cell differentiated toward hepatocytes strongly expressed these receptors. These results indicated microenvironment determine the fate of progenitor cell differentiation.
2) The roles of bone marrow cells (BMCs) in hepatic regeneration and carcinogenesis are still unknown. We analyzed whether oval cells are derived from BMCs and whether preneoplastic nodules or HCCs originate from BMCs in the choline-deficient, ethionine-supplemented (CDE) diet rat model. To clarify the origin of constituent cells in the liver, we transplanted BMCs from green fluorescent protein (GFP)-transgenic female rats into male rats, which were then exposed to a CDE diet to induce hepatocarcinogenesis. Some oval cells showed both donor-derived GFP expression and the recipient-specific Y chromosome, indicating that donor BMCs fused with recipient oval cells. Several preneoplastic nodules (precancerous lesions) were induced by CDE treatment. However, these preneoplastic nodules were not GFP-positive. In conclusion, this study has produced two major findings. First, BMCs fuse with some oval cells. Second, BMC-fused oval cells and BMCs might not have malignant potential in the CDE-treated rat model.
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Report
(4 results)
Research Products
(61 results)
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[Journal Article] Increased expression of thioredoxin-1, vascular endothelial growth factor, and redox factor-1 is associated with poor prognosis in patients with liver metastasis from colorectal cancer2008
Author(s)
Terumasa, Noike, Shiro, Miwa, Junpei, Soeda, Akira, Kobayashi, Shinichi, Miyagawa
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Journal Title
Hum Pathol. Feb 39(2)
Pages: 201-8
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model2008
Author(s)
Koji, Kubota, Junpei, Spada, Ryousuke, Misawa, Motohiro, Mihara, Shiro, Miwa, Hirohiko, lse, Masafumi, Takahashi, Shinichi, Miyagawa
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Journal Title
Carcinogenesis. Feb 29(2)
Pages: 448-54
Description
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[Journal Article] Is major hepatectomy with pancreatoduodenectomy justified for advanced biliary malignancy?2007
Author(s)
Shiro, Miwa., Akira, Kobayashi., Yasuhiko, Akahane., Takenari, Nakata., Motohiro, Mihara., Kei, Kusama., Shinichiro, Ogawa., Junpei, Soeda., Shinichi, Miyagawa
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Journal Title
J Hepatobiliary Pancreat Surg 14(2)
Pages: 136-41
Description
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[Journal Article] Kei Kusama, Shinichiro Ogawa and Junpei Soeda. Radical surgery for advanced squamous cell carcinoma of the gallbladder : a report of three cases, including a 10-year survivor2007
Author(s)
Akira, Kobayashi, Shinichi, Miyagawa, Shiro, Miwa, Kazuhiko, Nomura, Takenari, Nakata, Motohiro, Mihara
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Journal Title
Hepatogastroenterology. Mar 54(74)
Pages: 350-3
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Detection of hepatic metastases from colorectal carcinoma : comparison of histopathologic features of anatomically resected liver with results of preoperative imaging2007
Author(s)
Kazuhiko, Nomura, Masumi, Kadoya, Kazuhiko, Ueda, Yasunari, Fujinaga, Shiro, Miwa, Shinichi, Miyagawa
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Journal Title
J Clin Gastroenterol. Sep 41(8)
Pages: 789-95
Description
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[Journal Article] Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery.2006
Author(s)
Shiro, Miwa, Shinichi, Miyagawa, Akira, Kobayashi, Yasuhiko, Akahane, Takenari, Nakata, Motohiro, Mihara, Kei, Kusama, Junpei, Soeda, Shinichiro, Ogawa
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Journal Title
J Gastroenterol. Sep 41(9)
Pages: 893-900
NAID
Description
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[Presentation] 肝門部胆管癌の術式决定の検討2007
Author(s)
三輪史郎, 他
Organizer
第19回日本肝胆膵外科学会学術集会
Place of Presentation
パシフィコ横浜
Year and Date
2007-06-07
Description
「研究成果報告書概要(和文)」より
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[Presentation] 肝門部胆管癌に対する治療成績2006
Author(s)
三輪史郎, 他
Organizer
第61回日本消化器外科学会総会
Place of Presentation
パシフィコ横浜
Year and Date
2006-07-14
Description
「研究成果報告書概要(和文)」より
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[Presentation] 肝門部胆管癌の外科治療2006
Author(s)
三輪史郎, 他
Organizer
第106回日本外科学会総会
Place of Presentation
東京国際フォーラム
Year and Date
2006-03-29
Description
「研究成果報告書概要(和文)」より
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[Presentation] 胆管細胞癌の予後因子と治療戦略2005
Author(s)
三輪史郎, 他
Organizer
第60回日本消化器外科学会総会
Place of Presentation
東京高輪プリンスホテル
Year and Date
2005-07-21
Description
「研究成果報告書概要(和文)」より
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