| Project/Area Number |
16390209
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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 |
Gastroenterology
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| Research Institution | National University Corporation Tottori University |
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Principal Investigator |
SHIOTA Goshi Tottori University, Graduate School of Medical Sciences, Professor, 大学院・医学系研究科, 教授 (70263457)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Kanzo Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (40113196)
SHIGEMASA Yoshihiro Tottori University, Trustee, 理事 (00032029)
MORIMOTO Minoru Tottori University, Research senter for Bioscience and Technology, Associate Professor, 生命機能研究支援センター, 助教授 (10273880)
TAJIMA Fumihito Tottori University, University hospital, Associate Professor, 医学部附属病院, 講師 (60335528)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2004: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | stem cell / bone marrow / mesenchymal stem cell / hepatocytet / cytokine / liver regeneration treatment / demethylation agent / HDAC inhibitor / TERT / 骨髄間葉系細胞 / 臍帯血幹細胞 / HDAC抑制剤 / アルブミン |
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| Research Abstract |
For the purpose of development of liver regeneration therapy, we attempted to develop the novel methods, by which human mesenchymal stem cells (MSCs) can be differentiated to mature hepatocytes. We used bone marrow-derived MSCs and cord blood-derived MSCs.
1.Study by using bone marrow-derived MSCs
Using UE7T-13 cells, human bone marrow-derived MSCs which were retrovirally infected with human papilloma virus E7 and human telomerase reverse transcriptase (hTERT), 40 conditions of several cytokines, 5-azacytidine and type IV collagen coating were examined on hepatic differentiation of UE7T-13 cells. As a result, the optical condition for differentiation is type IV collagen-coating/aFGF/bFGF/HGF. By this condition, expression of hepatocyte-specific genes was highest. In addition, glycogen synthesis and urea synthesis was also greatly promoted by this treatment. Under this circumstance, WISP1 and WISP2 were down-regulated. Knockdown of WISP1 and WISP2 by siRNA also greatly enhanced hepatic differentiation of of MSCs.
2.Study by using cord blood-derived MSCs
Using UCBTERT-21 cells, human cord blood-derived MSCs which were retrovirally infected with human telomerase reverse transcriptase (hTERT), 8 conditions of several cytokines, 5-azacytidine, HDAC inhibitor were examined on hepatic differentiation of UCBTERT-21 cells. As a result, the optical condition for differentiation is 5-azacytidine/HGF/aFGF/OSM. By this condition, expression of hepatocyte-specific genes was highest. In addition, glycogen syntheisis and urea syntheisis was also greatly promoted by this treatment. Under this circumstance, Wnt signal was down-regulated. Knockdown of fzd8, the receptor of Wnt, WISP1 also greatly enhanced hepatic differentiation of of MSCs.
These results indicated new findings of hepatic differentiation of MSCs ; and contribute to the development of expanding and differentiation-promoting system ex vivo for liver regeneration.
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