| Project/Area Number |
17390353
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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 | Sapporo Medical University |
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Principal Investigator |
MITAKA Toshihiro Sapporo Medical University, Cancer Research Institute, Professor (50231618)
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| Co-Investigator(Kenkyū-buntansha) |
KIKKAWA Yamato Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Assistant Professor (20274227)
KON Junko Sapporo Medical University, Cancer Research Institute, Instructor (40398318)
ICHINOHE Norihisa Sapporo Medical University, Cancer Research Institute, Research Associate (80452978)
MIZUGUCHI Toni Sapporo Medical University, Medical School, Assistant Professor (30347174)
HIRATA Koichi Sapporo Medical University, Medical School, Professor (50136959)
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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 |
¥16,900,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2006: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2005: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | Regenerative medicine / Small hepatocytes / Henatic organoid / Differentiation / Proliferation / Hepatic progenitor cells / human hepatic progenitor cells / Bile duct formation / オーバル細胞 / CD44 / 幹細胞 / 肝臓 / 人工肝臓 / 成熟化 / ヒト |
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| Research Abstract |
We have reported that CD44 is specifically expressed in rat small hepatocytes and that CD44^+ hepatocytes transiently appear in injured rat livers. Using a specific antibody, we sorted CD44^+ cells from galactosamine-treated rat livers and cultured them. The phenotypes and gene expression of the cells were similar to those of cultured SHs and the ^+ cells could differentiate into hepatocytes (J Hepatol, 2006). In addition, some Thy1^+ cells that appeared in the galactosamine-treated livers could differentiate into + SHs and mature into hepatocytes. When the Thyl+ and CD44^+ cells were transplanted into livers treated with retrorsine/PH, they could survive and proliferate to form hepatic foci in the recipient livers. Furthermore, when cultured SHs were transplanted into congenic rat livers treated with radiation/PH, the cells migrated into hepatic trabecules and the liver was partially repopulated by the donor cells (Liver Transplant, 2006). Rat SHs cultured in hyaluronic acid (HA ; ligand for CD44)-coated dishes and serum-free medium could selectively proliferate with hepatic functions (Nature Protocols, 2007) and this method could be applied for the isolation of human SHs from normal liver tissues, which were surgically resected from patients with informed consent. The number of human SHs increased about 100-fold within 3 weeks and the cells showed hepatic characteristics such as albumin secretion (Cell Transplant, 2008). Furthermore, we found that the proliferation of rat SHs was enhanced by follistatin produced by SHs to inhibit the action of activin A, which is secreted by mature hepatocytes. On the other hand, we succeeded in reconstructing functional hepatic tissues by stacking up two-dimensional tissues composed of rat SHs (FASEB J, 2006). In addition, we could culture normal rat biliary epithelial cells for a long term and reconstruct functional bile ductules between collagen gels (Am J Pathol, 2008).
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