Transplanted isolated hepatocytes: effect of partial hepatectomy on proliferation of long-term syngeneic implants in rat spleen

Gupta, Sanjeev; Johnstone, R.; Darby, H.; Selden, Clare; Price, Y. E.; Hodgson, H. J. F.

doi:10.3109/00313028709065131

Cited by 29 publications

(7 citation statements)

References 8 publications

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“…Attempts to develop mice with humanized livers have taken various different approaches, beginning with studies in which isolated hepatocytes were injected directly into the hepatic portal vein (Matas et al, 1976; Shafritz and Oertel, 2011); to later studies which employ primary hepatocytes transplanted into the spleen that migrate to the liver and successfully engraft into the hepatic parenchyma (Gupta et al, 1987; Shafritz and Oertel, 2011). However, relatively little repopulation occurs under these conditions, and once these cells reached a density of ≈1–2% of total hepatic mass obstruction of liver sinusoids occurred resulting in portal hypertension and hepatic infarction (Shafritz and Oertel, 2011).…”

Section: Animal Models Of Alcohol Ingestionmentioning

confidence: 99%

Rodent models of alcoholic liver disease: Of mice and men

Brandon-Warner

Schrum

Schmidt

et al. 2012

Alcohol

113

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Alcoholic liver disease (ALD) is a major cause of acute and chronic liver disease worldwide. The progressive nature of ALD is well described however the complex interactions under which these pathologies evolve remain to be fully elucidated. Clinically there are no clear biomarkers or universally accepted, effective treatment strategies for ALD. Experimental models of ALD are an important component in identifying underlying mechanisms of alcohol-induced injury to develop better diagnostic markers, predictors of disease progression, and therapeutic targets to manage, halt, or reverse disease progression. Rodents remain the most accessible model for studying ALD pathology. Effective rodent models must mimic the natural history of ALD while allowing examination of complex interactions between multiple hepatic, and non-hepatic, cell types in the setting of altered metabolic or oxidative/nitrosative stress, inflammatory responses, and sensitivity to cytotoxic stress. Additionally, mode and duration of alcohol delivery influences hepatic response and presents unique challenges in understanding disease pathology. This review provides an overview of rodent models of ALD, their strengths and weaknesses relative to human disease states, and provides insight of the potential to develop novel rodent models to simulate the course of human ALD.

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Section: Animal Models Of Alcohol Ingestionmentioning

confidence: 99%

Rodent models of alcoholic liver disease: Of mice and men

Brandon-Warner

Schrum

Schmidt

et al. 2012

Alcohol

113

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“…In the 1980’s, primary isolated hepatocytes were transplanted into a variety of ectopic sites, including the dorsal fat pad (Jirtle et al 1980), spleen (Kusano and Mito, 1982), peritoneal cavity (Demetriou et al, 1986) and under the renal capsule (Ricordi et al, 1989). The cells survived to varying degrees in these sites and demonstrated hepatic morphology and function, including modest proliferation after inducing liver regeneration (Jirtle and Michalopoulos, 1982; Gupta et al, 1987). Studies during the past 15 years have clearly established that the liver can be repopulated by transplanted hepatic cells with restoration of normal structure and function and these studies will be the subject of this review.…”

Section: Introductionmentioning

confidence: 99%

Model systems and experimental conditions that lead to effective repopulation of the liver by transplanted cells

Shafritz

Oertel

2011

The International Journal of Biochemistry & Cell Biology

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In recent years, there has been substantial progress in transplanting cells into the liver with the ultimate goal of restoring liver mass and function in both inherited and acquired liver diseases. The basis for considering that this might be feasible is that the liver is a highly regenerative organ. After massive liver injury or surgical removal of two-thirds or more of the liver tissue, the organ can restore its mass with completely normal morphologic structure and function. It has also been found under highly selective conditions that transplanted hepatocytes can fully repopulate the liver and cure a metabolic disorder or deficiency state. Fetal liver cells can also substantially repopulate the normal liver, and it is hoped in the future that effective repopulation will be achievable with cultured cells or cell lines, pluripotent stem cells from other somatic tissues, embryonic stem cells, or induced pluripotent stem cells, which can now be generated in vitro by a variety of methods. The purpose of this review is to present the major systems that have been used for liver repopulation, the variables involved in obtaining successful repopulation and what has been achieved in these various systems to date with different cell types.

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“…Paper IV describes the first clinical application of partial hepatectomy preconditioning, a technique that improves hepatocyte engraftment and repopulation in animal models (106)(107)(108)(109)(110)(111). We show that partial hepatectomy induces a robust release of hepatocyte growth factor, and that transplantation of less than 5% of the liver mass induces a strong clinical effect.…”

Section: Concluding Remarks and Future Challengesmentioning

confidence: 98%