| Project/Area Number |
14370344
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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 |
General surgery
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
ATSUSHITA Michiaki Hokkaido Univ., School of Med., Professor, 医学部, 教授 (20250425)
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| Co-Investigator(Kenkyū-buntansha) |
TODO Satoru Hokkaido Univ., Grad.School of Med., Professor, 大学院・医学研究科, 教授 (60136463)
KAMACHI Hirofumi Hokkaido Univ., Grad.School of Med., Instructor, 大学院・医学研究科, 寄附講座・教員 (60374237)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | hepatic support / hybrid artificial liver / hepatocyte transplantation / small hepatocyte / hepatic regeneration / hepatocyte ploidy / biodegradable honeycomb patterned film / 増殖 / 細胞移植 / 人工肝臓 / in vitro増殖 / 肝特異機能 / 凍結保存 |
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| Research Abstract |
This project was aimed to make a fundamental investigation for developing hepatic support therapies as a hybrid artificial liver and/or hepatocyte transplantation using small hepatocytes with high activities of proliferation.
(1)In the study for evaluating proliferative activity of small hepatocytes and the role of small hepatocytes in hepatic regeneration after 70% resection of the liver, small hepatocytes showed high proliferative activity with an increase in DNA amount four times in two weeks and an analysis of nuclear ploidy of hepatocyte showed small hepatocytes play a supplying role for a deficiency of adult hepatocytes in rat model.
(2)In the studies for the investigation for suitable environment for hepatocyte culture before use, hepatocyte culture on a honeycomb patterned biodegradable porous film and formation of small hepatocyte spheroid were investigated. The degree of spreading of hepatocyte was enhanced with decrease of the pore size (〜10μm) and partial hydrolysis of the fi
… More
lm surface enhanced the migration and spheroid formation of the cultured hepatocyte. In a shaking culture of 67rpm, small hepatocytes start to aggregate in three hours and became spheroids approximate 50〜80μm in diameter in six hours. Shape of the spheroics has been kept for 10 days in culture.
(3)In the study for small hepatocyte transplantation into analbuminemia rat through portal vein, serum albumin elevated 2.5 times in four weeks. Massive albumin positive cells were observed in the immunohistological staining of the transplanted liver. Small hepatocytes are considered as a promising candidate cell for cell transplantation and for a hybrid artificial liver.
(4)Small hepatocytes possess high proliferative activity, but they are not immortalized cells. Therefore gene induction was investigates as a basic study for immortalization of small hepatocytes. An effective method of gene induction as of around 100% was found in singularized islets.
It was concluded that small hepatocytes were suggested to be a good cell source of hepatic support therapies as a hybrid artificial liver and/or hepatocyte transplantation. Less
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