| Project/Area Number |
11671299
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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 |
Digestive surgery
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| Research Institution | National Children's Medical Research Center |
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Principal Investigator |
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)
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| Co-Investigator(Kenkyū-buntansha) |
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)
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)
SUZUKI Seiichi National Children's Medical Research Center, Derector, 小児医療研究センター・実験外科生体工学部, 部長 (00111386)
三谷 匡 国立小児病院, 小児医療研究センター・実験外科生体工学部, 科技庁開放融合研究員
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | in utero manipulation / liver / rat / gene transduction / fetal therapy / amniotic epithelial cells / cell transplantation / cell therapy |
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| Research Abstract |
Rat fetal liver is a good model for choice to develop cell transplantation because the liver is under developmental and proliferative stage and visible through uteric memebrane. Amniotic epithelial cells, which we chose as donor cell this time, are proposed to be possible gene carrier into neural and hepatic tissue. The advantages of the cells are that 1) ethical problem are few, 2) there are neural and hepatic stem-like cells, 3) cells can be stored frozen, and 4) cells survive for relatively long-term. However, mass transplantation of amniotic cells via portal vein may cause embolism and the cells intrinsically proliferate only by two or three division in vitro. Therefore, we performed transplantation of amniotic cells into fetal liver. 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 fetuses at early stage(day 14), suggesting that telomerase transfection may accelerate cell proliferation. After cell transplantation(lacZ-transfected, 1〜8x10^6/10〜25μ1)to the liver of fetus(day18.5-20.5), 24-85% of the rats survived to be born. The transplanted cells were detectable in the liver at least 14 days after birth. The lacZ-positive cell remained longer with amniotic cell transplantation than direct injection of Ad-lacZ vector into fetal liver at the same stage. Therefore, present In-Utero-Manipulation will be useful strategy for cell mediated gene therapy for congenital liver disease.
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