| Project/Area Number |
14207026
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
HORIE Yoshinori (2004) Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (70229227)
石井 裕正 (2002-2003) 慶應義塾大学, 医学部, 教授 (20051500)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Shinzo Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (30177448)
SAITO Hidetsugu Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (80186949)
TOMITA Kengo Keio University, Department of Medicine, Research Assistant, 医学部, 助手 (50317129)
INOKUCHI Sayaka Keio University, Department of Medicine, Research Assistant, 医学部, 助手 (00383711)
OKANO Hideyuki Keio University, Department of Medicine, Professor, 医学部, 教授 (60160694)
堀江 義則 慶應義塾大学, 医学部, 専任講師 (70229227)
東 俊文 慶應義塾大学, 医学部, 専任講師 (00222612)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000)
Fiscal Year 2004: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2003: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2002: ¥31,720,000 (Direct Cost: ¥24,400,000、Indirect Cost: ¥7,320,000)
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| Keywords | side population cell / stem cell autotransplantation / collagen gel sandwich configuration / hepatic differentiation induction method / 肝細胞分化 / 脾臓 / 自家細胞移植 / 肝再生 / 細胞融合 / 移植医療 / 肝硬変 / 肝不全 / 初代培養肝細胞 / コラーゲンゲル / 幹細胞 |
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| Research Abstract |
1. Hepatic differentiation induction method in vitro
In an effort to reconstruct the hepatocyte function and cellular polarity normally found in the liver, adult rat hepatocytes were sandwiched between two layers of hydrated collagen matrix. Functionally, sandwiched hepatocytes maintained the secretion of albumin, the expression of liver specific proteins and the distribution of actin filaments, whereas the cells cultured on single layer of collagen gel decreased the albumin secretion, the liver specific proteins and showed abnormal formation of actin stress fibers and cell spreading. Overlaying a second layer of collagen gels on the hepatocytes that had been cultured on a single gel reversed the cell spreading, reduced actin stress fibers and recovered the liver specific protein expressions.
Bone marrow cells could differentiate into hepatocytes when they co-cultured with primary cultured hepatocytes in collagen gel sandwich indicating that hepatocytes cultured in collagen gel sandwich was functionally good enough to induce differentiation of bone marrow cell into hepatocytes.
2. SP cells
We could successfully induce SP cells derived from liver and bone marrow transdifferentiation into hepatocytes in vitro and in vivo. Splenic SP cells have a remarkable capacity for hepatic differentiation, as they were co-cultured with primary cultured hepatocytes in collagen gel. It is our great surprise that the prevalence of SP cells in spleen is 5 to 10 times higher than in bone marrow. Our results indicated that splenic-SP cells might have the potential to transdifferentiate into hepatocytes. Since the prevalence of SP cells in spleen is much higher than in bone marrow, total amount of SP cells could be much larger. Thus the spleen could have the highest prevalence of SP cells and spleen could provide an alternative source of stem cell for stem cell transplantation into liver.
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