Search for facto s that induce transdifferentiation from liver stem cell to epitheial cells of digestive gland and development with tissue engineering
Project/Area Number |
15300154
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomedical engineering/Biological material science
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Research Institution | Akita University |
Principal Investigator |
SUGIYAMA Toshihiro Akita University, School of Medicine, Professor, 医学部, 教授 (00127242)
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Co-Investigator(Kenkyū-buntansha) |
UENO Yasuharu Akita University, School of Medicine, Assistant Professor, 医学部, 助手 (60375235)
亀田 隆 秋田大学, 医学部, 講師 (00301119)
寺田 邦彦 秋田大学, 医学部, 助教授 (60197796)
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Project Period (FY) |
2003 – 2005
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Project Status |
Completed (Fiscal Year 2005)
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Budget Amount *help |
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥7,600,000 (Direct Cost: ¥7,600,000)
|
Keywords | liver stem cell / growth factor / collagen / β-cell / oncostatin M / HSL cell / 細胞移植 / 放線菌 |
Research Abstract |
Organ restitution using somatic stem cells is of great clinical interest. Recent advances in the field of tissue engineering have demonstrated that the use of collagen matrices as scaffolds facilitates tissue reconstruction. Here we have examined the efficacy of transplantation of hepatic stem-like (HSL) cells, a previously established liver epithelial cell line with a potential for differentiation, using collagen scaffolds. To this end, HSL cells were transplanted into Nagase's analbuminemic rat with spongy or gelatinous type I collagen matrices. Consequently, immunohistochemical analyses and genomic PCR experiments revealed engraftment of the transplanted cells. Furthermore, the levels of serum albumin in recipient rats were found to increase up to 2.5 fold relative to controls after transplantation. These findings suggest that HSL cells are able to differentiate into functional hepatocytes in vivo, and that biodegradable collagen matrices may enhance this phenomenon by providing an appropriate microenvironment for hepatocytic repopulation. To apply cell transplantation for treatment of diabetes mellitus, a sufficient number of beta-cell sources are required. In the present study, we examined whether HSL cells could be a potential beta-cell source. RT-PCR analysis revealed that a series of transcriptional factors involved in differentiation of pancreatic endocrine cells was induced by the treatment with sodium butyrate and betacellulin. HSL cells obtained from adult normal liver also have the potential to differentiate into pancreatic endocrine cells in vitro. HSL cells may be one of the potential beta-cell sources for cell transplant therapy for insulin-dependent diabetes.
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Report
(4 results)
Research Products
(89 results)
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[Journal Article] Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin receptor A in cardiovascular morphogenesis.2005
Author(s)
Kanzaki-Kato N., Tamakoshi T., Fu Y., Chandra A., Itakura T., Uezato T., Tanaka T., Clouthier D.E., Sugiyama T., Yanagisawa M., Miura N.
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Journal Title
Cardiovasc.Res. 65
Pages: 711-718
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes.2005
Author(s)
Okaya A., Kitanaka J., Kitanaka N., Satake M., Kim Y., Terada K., Sugiyama T., Takemura M., Fujimoto J., Terada N., Miyajima A., Tsujimura T.
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Journal Title
Am.J.Pathol. 166
Pages: 709-719
Description
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[Journal Article] The Wilson disease protein ATP7B resides in the late endosomes with Rab7 and the Niemann-Pick C1 Protein.2005
Author(s)
Harada M., Kawaguchi T., Kumemura H., Terada K., Ninomiya H., Taniguchi E., Hanada S., Baba S., Maeyama M., Koga H., Ueno T., Furuta K., Suganuma T., Sugiyama T., Sata M.
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Journal Title
Am.J.Pathol. 166
Pages: 499-510
Description
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[Journal Article] Restoration of copper metabolism and rescue of hepatic abnormalities in LEC rats, an animal model of Wilson's disease, by expression of human ATP7B gene.2004
Author(s)
Yan M.Y., Miyoshi I., Hirabayashi M., Su M., Mototani Y., Okamura T., Terada K., Ueda M., Enomoto K., Sugiyama T., Kasai N.
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Journal Title
Biochim.Biophys.Acta 1690
Pages: 208-219
Description
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[Journal Article] Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) in human hepatocellular carcinoma.2004
Author(s)
Sugeno H., Takebayashi Y., Higashimoto M., Ogura Y., Shibukawa G., Kanzaki A., Terada K., Sugiyama T., Watanabe K., Katoh R., Nitta Y., Fukushima T., Koyama Y., Inoue N., Sekikawa K., Ogawa K., Sato Y., Takenoshita S.
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Journal Title
Anticancer Res. 24
Pages: 1045-1048
Description
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[Journal Article] Prognostic value of the Cu-transporting ATPase in ovarian carcinoma patients receiving cisplatin-based chemotherapy.2004
Author(s)
Nakayama K., Kanzaki A., Terada K., Mutoh M., Ogawa K., Sugiyama T., Takenoshita S., Itoh K., Yaegashi N., Miyazaki K., Neamati N., Takebayashi Y.
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Journal Title
Clin.Cancer Res. 10
Pages: 2804-2811
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Peroxisome proliferator-activated receptor gamma ligands, 15-deoxy-Delta12,14-prostaglandin J2, and ciglitazone, induce growth inhibition and cell cycle arrest in hepatic oval cells.2004
Author(s)
Cheng J., Nakamura H., Imanishi H., Liu W., Morisaki T., Sugiyama T., Hada T.
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Journal Title
Biochem.Biophy.Res.Commun. 322
Pages: 458-464
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Application of collagen scaffolds for hepatic stem-like cell transplantation.2004
Author(s)
Ueno Y., Terada K., Nagai H., Watanabe G., Ishikawa K., Yoshikawa K., Hirayama Y., Endo E., Kameda T., Liu Y., Sugiyama T.
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Journal Title
Akita J.Med. 31
Pages: 113-119
NAID
Description
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[Journal Article] Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages.2003
Author(s)
Okumura K., Nakamura K., Hisatomi Y., Nagano K., Tanaka Y., Terada K., Sugiyama T., Umeyama K., Matsumoto K., Yamamoto T., Endo F.
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Journal Title
Hepatology 38
Pages: 104-113
Description
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[Journal Article] Epimorphin is involved in differentiation of rat hepatic stem-like cells through cell-cell contact.2003
Author(s)
Miura K., Nagai H., Ueno Y., Goto T., Mikami K., Nakane K., Yoneyama K., Watanabe D., Terada K., Sugiyama 'T., Imai K., Senoo H., Watanabe S.
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Journal Title
Biochem.Biophys.Res.Commun. 311
Pages: 415-423
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Wilson disease protein ATP7B is localized in the late endosomes in a polarized human hepatocyte cell line. Int.2003
Author(s)
Harada M., Kumemura H., Sakisaka S., Shishido S., Taniguchi E., Kawaguchi T., Hanada S., Koga H., Kumashiro R., Ueno T., Suganuma T., Furuta K., Namba M., Sugiyama T., Sata M.
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Journal Title
Int.J.Mol.Med. 11
Pages: 293-298
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of copper-transporting P-type adenosine triphosphatase in human esophageal carcinoma.2003
Author(s)
Higashimoto M., Kanzaki A., Shimakawa T., Konno S., Naritaka Y., Nitta Y., Mori S., Shirata S., Yoshida A., Terada K., Sugiyama T., Ogawa K., Takebayashi Y.
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Journal Title
Int.J.Mol.Med. 11
Pages: 337-341
Description
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[Journal Article] Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin.2003
Author(s)
Miyashita H., Nitta Y., Mori S., Kanzaki A., Nakayama K., Terada K., Sugiyama T., Kawamura H., Sato A., Morikawa H., Motegi K., Takebayashi Y.
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Journal Title
Oral Oncol. 39
Pages: 157-162
Description
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