2001 Fiscal Year Final Research Report Summary
A DEVELOPMENT OF THE HEPATOCYTE TRANSPLANTATION THERAPY USING THE LIVER STEM-LIKE CELLS DIFFERENCIATED BY CELL BIOTHECNOLOGY
| Project/Area Number |
11557091
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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 | 展開研究 |
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| Research Field |
Digestive surgery
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| Research Institution | Gunma University Faculty of Medicine |
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Principal Investigator |
KOGURE Kimitaka Gunma University Faculty of Medicine, Assistant Professor, 医学部, 講師 (80143220)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Itaru Institute for Molecular and Cellular Regulation Gunma University, Department of Cell Biology, Professor, 生体調節研究所, 教授 (60143492)
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| Project Period (FY) |
1999 – 2001
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| Keywords | liver stem-like cell / hepatocyte transplantation / artificial liver / TGF-β / activin A / gene transfer / dominant negative receptor of TGF-β and activin A / adenovirus vector |
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| Research Abstract |
Augmentation of liver regeneration, with an artificial support to maintain liver function necessary for survival, would be beneficial for the treatment of fulminant hepatic failure caused by viral infection and hepatic toxins. As well, massive hepatectomy in the treatment of hepatocellular carcinoma can be performed safely if the function of the remnant liver is effectively supported by the alternative livers. The present study was conducted to address this issue. For this purpose, we intended to develop the hepatocyte transplantation therapy from many types of the alternative livers. We completed the technology of efficiently extracting a stem-like liver cells from rat liver. The stem-like liver cells was proliferated and transplanted into the body of the rat after the differentiation of these cells. We constructed a few mm x 10 mm size of hepatic mass in the body of the rat by transplantation of the minimal hepatocytes. The hepatic mass showed the lobular structures encircled with th
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e sinusoidal components and survived over 3 months.
As a related experiment, we conducted the study to assess the role of transforming growth factor β (TGF-β) and activin(s) in the regulation of the mass of the liver. We eliminated TGF β or activin signaling in intact rat liver by adenovirus-mediated transfer of the gene encoding truncated type II TGF-β receptor (AdextTR) or truncated type II activin receptor (Adext AR). In AdextTR and Adext AR-treated rats, nuclear labeling with BrDU was significantly higher than that in AdextLacZ or saline treated rats. Immunoreactivity of TGF-β and activin A increased in the liver after the blockade of the activin or TGF-β signaling. These results indicate that blockade of the action of either TGF-β or activin leads to the initiation of DNA synthesis in intact liver (Hepatology, 2001 ; 34 : 918-925).
Aiming at the completion of the functional artificial hepatic mass in treating the patients of fulminant hepatic failure, the liver stem-like cells obtained from AdextTR and Adext AR-treated rats are cultured and proliferated and then transplanted into the body of the rat. Less
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Research Products
(26 results)
