Histidinemia in mice: A metabolic defect treated using a novel approach to hepatocellular transplantation

doi:10.1016/0270-9139(95)90063-2

Hepatology

Volume 21, Issue 5, May 1995, Pages 1405-1412

https://doi.org/10.1016/0270-9139(95)90063-2 Get rights and content

Abstract

Histidinemia in mice and in humans is an autosomal recessive disorder of histidine metabolism that leads to high-histidine levels in both plasma and urine and is caused by a lack of hepatic histidine-α-deaminase (histidase). We have used a novel approach to hepatocellular transplantation to effect a complete phenotypic cure of histidinemia in a mouse model. Mice lacking histidase were treated with isolated liver cells (approximately 18 × 10⁶ hepatocytes and 9 x 10⁶ nonparenchymal cells) from histidase-competent donors transplanted into the peritoneum (active transplant group). Recipient mice showed a dramatic decrease, by more than 75%, in urinary histidine levels from day one throughout the course of the experiment, resulting in levels within the normal range for wild-type mice. In comparison, there was no change in urinary histidine levels in the control group of histidase-deficient mice treated with isolated liver cells from mice lacking histidase (statistical comparison between the two groups, P < .003, two-way ANOVA). Histologically, ectopic liver tissue was seen in the peritoneum in association with abdominal wall, pancreas, and peritoneal connective tissue; immunohistochemical evidence showed expression of histidase in the ectopic liver tissue in the active transplant group. This report is the first to show complete correction of a defective biochemical phenotype achieved by hepatocellular transplantation.

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^☆: Supported by Action Research, London, England, and the Hammersmith and Queen Charlottes Special Health Authority, London, England.

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Histidinemia in mice: A metabolic defect treated using a novel approach to hepatocellular transplantation☆

Abstract

Biol Psychiatry

J Pediatr

Genomics

J Surg Res

J Biol Chem

Gastroenterology

Exp Cell Res

Disorders of histidine metabolism

Histidinemia: a biochemical variant or a disease?

J Am Coll Nutr

Speech and histidinemia: methodology and evaluation of four cases

Dev Med Child Neurol

A familial disturbance of histidine metabolism

N Engl J Med

Histidinaemia in mouse and man

Arch Dis Child

Assignment of histidaseregulating locus to chromosome 10 of the mouse

Biochem Genet

The biochemistry and genetics of histidinaemia in the mouse

Reversal of ischemic liver failure by intrasplenic liver cell transplantation

J Pediatr Surg

Intrasplenic hepatocyte transplantation in rats with experimental liver injury: morphological and morphometric studies

J Pathol

The pulmonary vascular bed as a site for implantation of isolated liver cells in inbred rats

Transplantation

Hepatocyte transplantation into the lung for treatment of acute hepatic failure in the rat

Transplant Proc

Transplantation of isolated hepatocytes into the pancreas

Eur Surg Res

Hepatocyte transplantation

Intraperitoneal hepatocyte transplantation: morphological results

Virchows Arch A Pathol Anat Histopathol

Restoration of liver function in Gunn rats without immunosuppression using transplanted microencapsulated hepatocytes

Hepatology

Evidence of metabolic activity of adult and fetal rat hepatocytes transplanted into solid supports

Transplantation

Intraperitoneal hepatocyte transplantation: morphologic findings and clinical relevance

Helv Chir Acta

Hepatocyte transplantation into spleen or solid supports: comparison of morphology, function, and proliferative response

Transplant Proc

High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study

J Cell Biol

Hepatocyte transplantation for enzyme deficiency disease in congenic rats

Transplantation