| Project/Area Number |
17590685
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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 | Nihon University |
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Principal Investigator |
MATSUMOTO Taro Nihon University, School of Medicine, Associate Professor (50366580)
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| Co-Investigator(Kenkyū-buntansha) |
MUGISHIMA Hideo Nihon University, School of Medicine, Professor (80183648)
FUKUDA Noboru Nihon University, Advanced Research Institute for Sciences and Humanities, Associate Professor (40267050)
MITSUMATA Masako Nihon University, School of Medicine, Professor (40064589)
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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 |
¥3,580,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Inrestinal regeneration / Regenerative Medicine / ES cell / CDX2 / Absorptive epithelial cell / 小腸不全 / CDX / 腸管上皮幹細胞 |
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| Research Abstract |
1. Transdifferentiation study of colon epithelial cells into intestinal epithelial cell phenotype.
We constructed colon epithelial cell line (HT29 cells) stably expressing CDX2 by lentivirus gene transfer system. The HT29 cells expressing CDX2 revealed that high expression of intestinal epithelial marker genes such as IAP, SI, hephaestin, and cadherin 17. These findings suggest that the HT29 cells expressing CDX2 transdifferentiate into intestinal epitheial cell phenotype.
2. Induction of intestinal tissue in mouse embryonic bodies
We examined whether mouse embryoid bodies (EB) can differentiate into functional gut in grafts under the kidney capsules. Transplantation of gut-like structures in EB under kidney capsules of immunodeficient mice induced formation of highly differentiated epithelium composed of absorptive cells and goblet cells in the grafts. Immunoreactivity for Musashi-1, a marker of intestinal stem cells, was detected in approximately 2% of the columnar epithelial cells in the grafts. These findings indicate that ES cells can differentiate into several epithelial cell lineages of gut, including intestinal stem cells.
3. Generation of mice expressing CDX2 in colon tissue
To generate mice over-expressing CDX2 in colon tissue, lentiviral vector encoded CDX2 was infected in colon tissue via the balloon catheter. Expression of CDX2 specifically in colon epithelium was detected by immunohistochemistry. CDX2-expressed colon epithelium revealed that villous-like structure, suggesting transdifferentiation of colon epithelium into absorptive epithelium.
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