Treatment of cirrhosis and liver failure in rats by hepatocyte xenotransplantation

Nagata, Hideo; Ito, Masahiro; Cai, Jiabing; Edge, Albert S.B.; Platt, Jeffrey L.; Fox, Ira J.

doi:10.1053/gast.2003.50065

Cited by 123 publications

(77 citation statements)

References 32 publications

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“…2 Animal studies on portal vein CT of isolated adult hepatocytes have shown improved hepatic function, and this suggests that support for patients with chronic liver failure is possible. 3 Initial clinical studies of adult hepatocyte CT have demonstrated that this procedure can be performed as a minimally invasive cell injection, but studies on the use of adult liver cells have shown various outcomes. Some major problems are associated with the use of adult human liver cells for transplantation.…”

mentioning

confidence: 99%

Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell-based therapy and case report on cell transplantation

et al. 2012

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Although hepatic cell transplantation (CT) holds the promise of bridging patients with end-stage chronic liver failure to whole liver transplantation, suitable cell populations are under debate. In addition to hepatic cells, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are being considered as alternative cell sources for initial clinical cell work. Fetal liver (FL) tissue contains potential progenitors for all these cell lineages. Based on the collagenase incubation of tissue fragments, traditional isolation techniques yield only a fraction of the number of available cells. We report a 5-step method in which a portal vein in situ perfusion technique is used for tissue from the late second trimester. This method results in the high viabilities known for adult liver vascular perfusion, addresses the low cell yields of conventional digestion methods, and reduces the exposure of the tissue to collagenase 4-fold. We used donated tissue from gestational weeks 18 to 22, Additional Supporting Information may be found in the online version of this article.

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confidence: 99%

Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell-based therapy and case report on cell transplantation

et al. 2012

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“…Porcine hepatocytes were as effective as syngeneic rat hepatocytes in the correction of the animal's liver functions. The survival of the animals was significantly improved and was equivalent in the animals treated with xenotransplant and those treated with syngeneic rat hepatocytes [Nagata et al, 2003]. The importance of this study is the fact that xenotransplants can be as effective as cells from the same species.…”

Section: Liver Pathologies and Therapiesmentioning

confidence: 86%

“…In a latest report, xenotransplants of porcine hepatocytes into a rat model of terminal cirrhosis displayed improvement in liver functions [Nagata et al, 2003]. Animals that received hepatocyte transplants showed significant improvement in their encephalopathy scores, plasma bilirubin and albumin, and ammonia levels compared with untreated controls.…”

Section: Liver Pathologies and Therapiesmentioning

confidence: 96%

Study of hepatocyte differentiation using embryonic stem cells

Lavon

Benvenisty

2005

J of Cellular Biochemistry

114

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The liver has many crucial functions including metabolizing dietary molecules, detoxifying compounds, and storing glycogen. The hepatocytes, comprising most of the liver organ, progressively modify their gene expression profile during the fetal development according to their roles in the different phases of development. Embryonic stem (ES) cells serve as a major tool in understanding liver development. These cells may also serve as a source of hepatic cells for cellular therapy. In this review, we aim to summarize the research that has been performed in the field of hepatocyte differentiation from mouse and human ES cells. We discuss the various methodologies for the differentiation of ES cells towards hepatic cells using either spontaneous or directed differentiation protocols. Although many protocols for differentiating ES cells to hepatic cells have been developed, the analysis of their status is not trivial and can lead to various conclusions. Hence, we discuss the issues of analyzing hepatocytes by means of the specificity of the markers for hepatocytes and the status of the cells as fetal or adult hepatocytes.

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“…6 Transplant of hepatocytes has been shown to significantly improve or correct prothrombin time, serum albumin and bilirubin levels, and survival in a rat model of terminal end-stage cirrhosis. 7,8 In addition, metabolic defects in bilirubin metabolism, albumin secretion, copper excretion, familial intrahepatic cholestasis, and tyrosinemia have been corrected by hepatocyte transplant. 8,9 Stem cell therapy is attractive for its potential to support tissue regeneration,as it requires minimally invasive procedures and shows few complications in liver diseases.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Baz

Demerdash²,

Kamel³

et al. 2018

Exp Clin Transplant

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Objectives: Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure. Materials and Methods: Undifferentiated human cord blood mesenchymal stem cells were isolated, propagated, and characterized by morphology, gene expression analysis, and flow cytometry of surface markers and in vitro differentiated into hepatocytelike cells. Rat hepatocytes were isolated by double perfusion technique. An animal model of chronic liver failure was developed, and undifferentiated human cord blood mesenchymal stem cells, in vitro hepatogenically differentiated mesenchymal stem cells, or freshly isolated rat hepatocytes were transplanted into a CCL4 cirrhotic experimental model. Animals were killed 3 months after transplant, and liver functions and histopathology were assessed. Results: Compared with the cirrhotic control group, the 3 cell-treated groups showed improved alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin levels, with best results shown in the hepatocyte-treated group. Histopathologic examination of the treated groups showed improved fibrosis, with best results obtained in the undif ferentiated mesenchymal stem cell-treated group. Conclusions: Both adult hepatocytes and cord blood mesenchymal stem cells proved to be promising candidates for cell-based therapy in liver regeneration on an experimental level. Improved liver function was evident in the hepatocyte-treated group, and fibrosis control was more evident in the undifferentiated mesenchymal stem cell-treated group.

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Treatment of cirrhosis and liver failure in rats by hepatocyte xenotransplantation

Cited by 123 publications

References 32 publications

Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell-based therapy and case report on cell transplantation

Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell-based therapy and case report on cell transplantation

Study of hepatocyte differentiation using embryonic stem cells

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