2005 Fiscal Year Final Research Report Summary
Clinical application of bioartifical liver support and heopatocyte transplantation using human hepatocytes
| Project/Area Number |
15591371
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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 |
General surgery
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| Research Institution | National Hospital Organization Nagasaki Medical Center Clinical Research Center |
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Principal Investigator |
FUJIOKA Hikaru National Hospital Organization, Nagasaki Medical Center, Clinical Research Center, Department of Function & Morphology, Director, 臨床研究センター, 機能形態研究部長 (00264226)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIBASHI Hiromi National Hospital Organization, Nagasaki Medical Center, Clinical Research Center, Clinical Research Center, Director, 臨床研究センター, 臨床研究センター長 (80127969)
YATSUHASHI Hiroshi National Hospital Organization, Nagasaki Medical Center, Clinical Research Center, Department of Therapeutic Research, Director, 臨床研究センター, 治療研究部長 (50360855)
NAKAMURA Minoru National Hospital Organization, Nagasaki Medical Center, Clinical Research Center, Department of Advanced Medical Research, Director, 臨床研究センター, 先端技術研究部長 (40217906)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Human hepatocyte / Bank of hepatocytes / Bioartificial liver / Hepatocyte transplantation / Gene transfer |
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| Research Abstract |
Liver transplantation improves the survival rate and quality of life for patients with life-threatening liver diseases. This therapy, however, is associated with several problems including significant morbidity, mortality and the shortage of liver donors. Therefore, the demand for clinical use of bioartificial liver and isolated hepatocytes. Unfortunately, the number of donor livers available for human hepatocyte isolation is limited. Other animal species have been suggested as a potential source of hepatocytes for these therapies. However, immunologic and physiologic barriers to cross-species use have yet to be overcome. In addition, there is another concern about zoonosis so that human hepatocytes shoud be used for these therapies.
The purpose of this study is to establish an efficient isolation and cryopreservation method for the human hepatocyte bank. In addition, efficiency of HVJ-liposome for gene transfer into porcine hepatocytes was investigated.
Results :
Human hepatocytes were harvested from 16 volunteers with metastatic liver tumors or hemangiomas using a modification of the two step-collagenase perfusion technique. The yield of freshly isolated hepatocytes averaged more than 8.5x10^6/liver gr.with 80% viability. The average viability of thawed hepatocytes that had been cryopreserved for 30days was 62% and plating efficiency was 40% in the solution of UW (University of Wisconsin) with human fresh frozen plasma (FFP). The use of UW solution and FFP significantly improved the viability and plating efficiency of cryopreserved human hepatocytes.
Now, we preserve 3.0x10^<10> human hepatocytes. Therefore, we can treat three patients with fatal liver failure. However, there have been no patients for the hepatocyte-based therapy during this study.
HVJ-liposome vector was safe and feasible modality for hepatocyte-directed gene transfer in pigs. It might be suitable for clinical hepatocyte-gene therapy trials.
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Research Products
(11 results)
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[Journal Article] Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways.2006
Author(s)
Yokoyama T, Komori A, Nakamura M, Takii Y, Kamihira T, Shimoda S, Mori T, Fujiwara S, Koyabu M, Taniguchi K, Fujioka H, Migita K, Yatsuhashi H, Ishibashi H
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Journal Title
Liver Int. 26(4)
Pages: 467-476
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis.2006
Author(s)
Nakamura M, Takii Y, Ito M, Komori A, Yokoyama T, Shimizu-Yoshida Y, Koyabu M, Matsuyama M, Mori T, Kamihira T, Daikoku M, Migita K, Yatsuhashi H, Nozaki N, Shimoda S, Ishibashi H
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Journal Title
J.Autoimmunity 26(2)
Pages: 138-145
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Immunosuppressant FK506 inhibits matrix metalloproteinase-9 induction in TNF-alpha-stimulated human hepatic stellate cells.2006
Author(s)
Migita K, Maeda Y, Abiru S, Nakamura M, Komori A, Yokoyama T, Takii Y, Mori T, Yatsuhashi H, Eguchi K, Ishibashi H
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Journal Title
Life Sci. 78(21)
Pages: 2510-2515
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis.2005
Author(s)
Nakamura M, Shimizu-Yoshida Y, Takii Y, Komori A, Yokoyama T, Ueki T, Daikoku M, Yano K, Matsumoto T, Migita K, Yatsuhashi H, Ito M, Masaki N, Adachi H, Watanabe Y, Nakamura Y, Saoshiro T, Sodeyama T, Koga M, Shimoda S, Ishibashi H
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Journal Title
J.Hepatol. 42(3)
Pages: 386-392
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhanced expression of type I interferon and toll-like receptor-3 in primary biliary cirrhosis.2005
Author(s)
Takii Y, Nakamura M, Ito M, Yokoyama T, Komori A, Shimizu-Yoshida Y, Nakao R, Kusumoto K, Nagaoka S, Yano K, Abiru S, Ueki T, Matsumoto T, Daikoku M, Taniguchi K, Fujioka H, Migita K, Yatsuhashi H, Nakashima M, Harada M, Ishibashi H
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Journal Title
Lab Invest. 85(7)
Pages: 908-920
Description
「研究成果報告書概要(欧文)」より
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