1999 Fiscal Year Final Research Report Summary
Development of cell therapy for hepatic failure due to dysfunction of hepatic parenchymal cells.
| Project/Area Number |
09470273
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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 |
Digestive surgery
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| Research Institution | National Children's Medical Research Center |
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Principal Investigator |
AMEMIYA Hiroshi National Children's Medical Research Center, General Director, 小児医療研究センター, センター長 (80009563)
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| Co-Investigator(Kenkyū-buntansha) |
LI Xiao-kang National Children's Medical Research Center, Researcher, 小児医療研究センター・実験外科生体工学部, 研究員 (60321890)
ENOSAWA Shin National Children's Medical Research Center, Division head, 小児医療研究センター・実験外科生体工学部, 室長 (40232962)
SUZUKI Seiichi National Children's Medical Research Center, Defector, 小児医療研究センター・実験外科生体工学部, 部長 (00111386)
OKUYAMA Torayuki National Children's Medical Research Center, Division head, 小児医療研究センター・先天異常研究部, 室長 (40177192)
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| Project Period (FY) |
1997 – 1999
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| Keywords | hepatocyte / differentiation / amniotic epithelial cells / CrmA / apoptosis / rat / cell transplantation / cell therapy |
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| Research Abstract |
Although there are various kinds of novel mdical technology at present, hepatic failure is one of serious diseases which have no fundamental therapies except for liver transplantation or only allopathy such as ultraviolet irradiation against hyperbilirubinemia etc, and some of the hepatic failure are due to congenital malfunction. In this research, we did basic investigation on hepatic cell therapy which may replace liver transplantation or innovate gene therapy. The main topics are 1) search off actor(s) or condition to develop or to maintain differentiated function of hepatocytes, 2) suitable cell types for hepatic cell transplantation, and 3) conditionhg of successful cell transplantation by gene transduction. We developed intra-gel culture of rat hepatocytes with rat fetus extract and rat plasma. This culture condition maintained drug metabolizing activity assessed by 7-ethoxycoumarin deethylation tip to for 7 days, as well as morphological feature of hepatocyte. For cell transplantation, we used amniotic epithelial cells from rat fetus. The certain population of the amniotic cells expressed albumin during culture period as was reported by human amniotic epithelial cells (J Hum Genet 45 171 2000). The cells can be stored frozen without marked impairment of viability. The cell division was 2.7 times at average and telomerase activity was detectable in the cells from feyses at early stage (day 14), suggesting that telomerase transfection may accelerate eell proliferation. To establish successful eell survival after transplantation, ants-apoptotic gene, CrmA, was transfected to hepatocytes, which showed long-term survival against rejection response.
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[Publications] Li XK, Fujino M, Guo L, Okuyama T, Funeshima N, Hashimoto M, Okabe K, Yaginuma H, Mikoshiba K, Enosawa S, Amemiya H, Suzuki S.: "Inhibition of Fas-mediated fulminant hepatitis in CrmA gene-transfected mice."Biochem Biophys Res Commun.. 273(1). 101-9 (2000)
Description
「研究成果報告書概要(欧文)」より
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