Heterotopically Transplanted Hepatocyte Survival Depends on Extracellular Matrix Components

Ohashi, Kazuhiko; Kay, Mark A.; Kuge, Hiroyuki; Yokoyama, Takashi; Kanehiro, Hiromichi; Hisanaga, Michiyoshi; S, Ko; Nagao, Mitsuo; Sho, Masayuki; Nakajima, Yoshiyuki

doi:10.1016/j.transproceed.2005.11.049

Cited by 11 publications

(14 citation statements)

References 11 publications

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“…Consistent with these earlier findings Tokyo Women's Medical University, Tokyo, recently reported that both the poor initial hepatocyte survival as well as the transient persistence of the hepatic tissue could be overcome by providing ECM components that are rich in laminin and type IV collagen (Matrigel, EHS‐ECMs) in studies where the hepatocytes were transplanted under the kidney capsule 16,17,21–23 . In these experiments, Engelbreth–Holm–Swarm extracellular matrix (EHS‐ECM) successfully recruited new blood vessels within and surrounding the transplanted area, which we believe contributed to the long‐term, stable persistence of the hepatic tissue throughout the life span of the recipient mice 17,23 (see Fig. 1a).…”

Section: Engineering Liver Tissues Using Extracellular Matrix Componentssupporting

confidence: 80%

“…1): S76-S87 Liver tissue engineering S77 the kidney capsule. 16,17,[21][22][23] In these experiments, Engelbreth-Holm-Swarm extracellular matrix (EHS-ECM) successfully recruited new blood vessels within and surrounding the transplanted area, which we believe contributed to the long-term, stable persistence of the hepatic tissue throughout the life span of the recipient mice 17,23 (see Fig. 1a).…”

Section: Kidney Capsule Sitementioning

confidence: 93%

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Liver tissue engineering: The future of liver therapeutics

Ohashi

2008

Hepatology Research

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The applications derived from the concept of tissue engineering have spurred significant interest in the field of regenerative medicine as novel, next generation therapies. Due to a lack of treatment modalities for patients suffering from many forms of liver diseases, recent studies have touted that engineering hepatic tissues de novo in culture may be a viable method to address this therapeutic void. Liver tissue engineering is a new and emerging field in which a functional liver system is created in vivo using isolated hepatocytes and/or other cells types to treat acute and chronic liver diseases. Under circumstances in which a small, but functional liver tissue system could be engineered to provide the equivalent biological function proportional to a few percent of a normal, well-functioning liver, it would be possible to correct many disease phenotypes as a result of various forms of inherited metabolic deficiencies. Alternatively, hepatic tissues can be engineered rapidly to produce therapeutic effects allowing this approach to become an effective modality in the treatment of acute liver failure. Strategies to achieve high levels of hepatocyte survival and the development of methods to engineer a functional liver system in vivo will be discussed in this review.

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Section: Engineering Liver Tissues Using Extracellular Matrix Componentssupporting

confidence: 80%

Section: Kidney Capsule Sitementioning

confidence: 93%

Liver tissue engineering: The future of liver therapeutics

Ohashi

2008

Hepatology Research

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“…Hepatocytes were isolated from C57Bl/6 wild-type mice using a collagenase perfusion method as previously described (13)(14)(15)(16). The recipient FIX knock-out (FIX-KO) mice, syngeneic to donor mice (17), were transplanted with the isolated hepatocytes (1.5ϫ10 6 cells in 200 L) into the liver through the inferior pole of the spleen (nϭ25).…”

mentioning

confidence: 99%

“…Using primary hepatocytes, our group has developed several innovative approaches to create a functional liver system under the kidney capsule or in subcutaneous locations (13,15,16,24,25), and we have clearly demonstrated that these ectopically engrafted hepatocytes also possess the ability for proliferation (13,16,26). This would be a significant benefit in the use of these hepatocytes, because most of the adult hemophilia B patients presented with chronic hepatitis B and/or C viral infection as a result of treatments with blood-borne contaminated plasma-derived FIX concentrates.…”

mentioning

confidence: 99%

Therapeutic Effects of Hepatocyte Transplantation on Hemophilia B

et al. 2008

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Hepatocyte transplantation offers an alternative therapeutic approach in the treatment of liver-related diseases. Hemophilia B is a bleeding disorder lacking factor IX (FIX) production in the liver, and achieving more than 1% coagulation activity results in significant improvement in the quality of life of the patients. The aim of this study was to investigate the efficacy of hepatocyte transplantation in the mouse model of hemophilia B. We transplanted isolated normal mouse hepatocytes into the liver of FIX knock-out mice. In some recipient mice, additional hepatocyte transplantations were performed 15 days after the first transplant. The recipient plasma FIX activities increased at 1% to 2% and persisted throughout the experimental period. An additional increase was achieved by the repeated transplantation. Close correlation between FIX messenger RNA levels of the liver and plasma FIX activity levels was observed. These results demonstrate that hepatocyte transplantation can provide therapeutic benefits in the treatment of hemophilia B.

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“…Specifically, we first engineered the hepatic tissue construct under the kidney capsules of mice by injecting primary hepatocytes mixed with Engelbreth-Holm-Swarm (EHS) gel. A higher engraftment rate of transplanted hepatocytes can be achieved by this method compared with conventional cell injection into the portal vein when the same numbers of hepatocytes are transplanted [ 60 – 62 ]. The engineered hepatic tissue demonstrated the same degree of liver-specific function, including the responsiveness to regenerative stimuli, protein secretion, and drug-metabolizing activity, as naïve liver [ 63 , 64 ].…”

Section: Cell Sheet Technology For Liver Tissue Engineeringmentioning

confidence: 99%

Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation

Tatsumi

Okano

2017

Curr Transpl Rep

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Purpose of ReviewWe will review the recent developments of cell sheet technology as a feasible tissue engineering approach. Specifically, we will focus on the technological advancement for engineering functional liver tissue using cell sheet technology, and the associated therapeutic effect of cell sheets for liver diseases, highlighting hemophilia.Recent FindingsCell-based therapies using hepatocytes have recently been explored as a new therapeutic modality for patients with many forms of liver disease. We have developed a cell sheet technology, which allows cells to be harvested in a monolithic layer format. We have succeeded in fabricating functional liver tissues in mice by stacking the cell sheets composed of primary hepatocytes. As a curative measure for hemophilia, we have also succeeded in treating hemophilia mice by transplanting of cells sheets composed of genetically modified autologous cells.SummaryTissue engineering using cell sheet technology provides the opportunity to create new therapeutic options for patients with various types of liver diseases.

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Heterotopically Transplanted Hepatocyte Survival Depends on Extracellular Matrix Components

Cited by 11 publications

References 11 publications

Liver tissue engineering: The future of liver therapeutics

Liver tissue engineering: The future of liver therapeutics

Therapeutic Effects of Hepatocyte Transplantation on Hemophilia B

Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation

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