Studies on the safety of intrasplenic hepatocyte transplantation: Relevance to ex vivo gene therapy and liver repopulation in acute hepatic failure

Sanjeev Gupta, Purnachandra R. Yerneni, Ravikumar P. Vemuru, Chang Don Lee, Edward L. Yellin, Kuldeep K. Bhargava

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Abstract

Hepatocytes transplanted into the host liver engraft promptly, retain normal function, and survive indefinitely. Although intrasplenic transplantation is effective in delivering hepatocytes to the liver, to define potentially limiting complications, we studied its safety in normal, cirrhotic, and partial portal vein-ligated rats. In normal rats, portal pressures increased severalfold after hepatocyte transplantation but returned to normal within 3 weeks. In contrast, in portal hypertensive rats with partial portal vein ligation or cirrhosis, portal pressures were either unchanged or increased less after hepatocyte transplantation. However, more transplanted cells migrated to the lungs along with a rise in right atrial pressures in portal hypertensive rats. Further quantitative studies using 111Indium-labeled hepatocytes showed that intrasplenic retention of transplanted hepatocytes was similar in all animal groups. Intrahepatic cell translocation was comparable in normal and cirrhotic rats, whereas fewer cells migrated to the liver in partial portal vein-ligated rats. The most remarkable difference, however, was significantly greater intrapulmonary translocation of hepatocytes in portal hypertensive rats, which was presumably related to portosystemic shunting. These results indicate that because intrasplenic hepatocyte transplantation induces only temporary portal hypertension in normal subjects, potential strategies to augment liver repopulation could include repeated cell transplantation. This should be useful for optimizing the results of ex vivo gene therapy, or other hepatocyte-based therapies. However, the hepatic and portal hemodynamic status requires careful evaluation in portal hypertensive or cirrhotic subjects if serious complications are to be avoided.

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalHuman Gene Therapy
Volume4
Issue number3
StatePublished - Jun 1993

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Acute Liver Failure
Genetic Therapy
Hepatocytes
Transplantation
Safety
Liver
Portal Vein
Portal Pressure
Atrial Pressure
Cell Transplantation
Portal Hypertension
Ligation
Fibrosis
Hemodynamics
Lung

ASJC Scopus subject areas

  • Genetics

Cite this

Studies on the safety of intrasplenic hepatocyte transplantation : Relevance to ex vivo gene therapy and liver repopulation in acute hepatic failure. / Gupta, Sanjeev; Yerneni, Purnachandra R.; Vemuru, Ravikumar P.; Lee, Chang Don; Yellin, Edward L.; Bhargava, Kuldeep K.

In: Human Gene Therapy, Vol. 4, No. 3, 06.1993, p. 249-257.

Research output: Contribution to journalArticle

Gupta, Sanjeev ; Yerneni, Purnachandra R. ; Vemuru, Ravikumar P. ; Lee, Chang Don ; Yellin, Edward L. ; Bhargava, Kuldeep K. / Studies on the safety of intrasplenic hepatocyte transplantation : Relevance to ex vivo gene therapy and liver repopulation in acute hepatic failure. In: Human Gene Therapy. 1993 ; Vol. 4, No. 3. pp. 249-257.
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