Splenic SP-cells offer the potential of autologous cell therapy aimed at liver regeneration.
| Project/Area Number |
15590687
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
KATO Shinzo (2004) Keio University, School of Medicine, lecturer, 医学部, 講師 (30177448)
東 俊文 (2003) 慶應義塾大学, 医学部, 専任講師 (00222612)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Toshifumi Keio University, School of Medicine, lecturer, 医学部, 講師 (00222612)
OKANO Hideyuki Keio University, School of Medicine, professor, 医学部, 教授 (60160694)
井口 清香 慶應義塾大学, 医学部, 助手 (00383711)
加藤 真三 慶應義塾大学, 医学部, 専任講師 (30177448)
石井 裕正 慶應義塾大学, 医学部, 教授 (20051500)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Auto-stem cell transplantation / Splenic side population / transdifferentiation / SP細胞 / 脾臓 / 肝臓 / 幹細胞移植 / 肝再生 / 自家細胞移植 / GFPトランスジェニックラット / 細胞融合 / 移植医療 / 肝硬変 / 肝不全 |
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| Research Abstract |
Cell therapy using hepatocytes or hepatocyte progenitor cells derived from autologous stem cells offers the possibility of restoring liver function, resulting in life-saving benefits for patients in danger of liver failure. The problem with stem cell therapy, though, is that the source of stem cells is limited. Splenectomies are performed on liver disease patients and ABO-incompatible liver transplantation recipients, and the results suggest that the spleen is a possible candidate source in auto-stem cell transplantation. In this study, we found that splenic side population (SP) cells offered a favorable source of stem cells from several points of view. First of all, it is easy to isolate cells from spleen tissue. Secondly, the spleen is notably rich in SP cells, where there is an almost 100 times greater amount of them than found in bone marrow, with them occurring at an almost 10 to 50 times higher frequency. Furthermore, most splenic SP cells are pluripotent. We found that they reconstituted lethally irradiated mouse bone marrow populations and transdifferentiated to hepatic cells. We have developed an efficient technique for culturing and growing SP cells over a 2-week period and inducing hepatic phenotypes in vitro. Co-culturing SP cells with primary cultured hepatocytes in a collagen gel sandwich configuration induced hepatic parenchymal cell phenotypes without fusion event, but not non-parenchymal cell phenotypes. The primary cultured hepatocytes consisted of pure parenchymal cells, so the factors secreted from those cells were capable of inducing the hepatic phenotype in stem cells. We propose that splenic SP-cells offer the potential to realize autologous cell therapy aimed at liver regeneration.
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Report
(3 results)
Research Products
(6 results)
