Massive repopulation of rat liver by transplantation of hepatocytes into specific lobes of the liver and ligation of portal vein branches to other lobes

Yaron Ilan, Namita Roy Chowdhury, Renu Prakash, Vinod Jona, Preeti Attavar, Chandan Guha, Kouji Tada, Jayanta Roy-Chowdhury

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

An important consideration in application of hepatocyte transplantation is whether the number of engrafted hepatocytes is sufficient to achieve the desired effect. Here we have evaluated the proliferative potential of transplanted primary hepatocytes during regeneration of hepatic lobes. Two million hepatocytes isolated from congeneic normal Wistar-RHA rats were injected into the main portal vein of deficient, jaundiced Gunn rats. The right branch of the portal vein was ligated 24 hr before hepatocyte transplantation (group A) or transiently clamped during hepatocyte injection (group B) or 24 hr after hepatocyte injection (group C). In these groups, the three lobes supplied by the right branch of the portal vein rapidly atrophied and disappeared in 4 days, whereas the remaining lobes proliferated, as shown by size increase and 5-bromo-2-deoxy-uridine uptake. Two control groups received 2 million (group D) or 20 million hepatocytes (group E) without ligation. Hepatocyte engraftment occurred in all groups. The greatest hypobilirubinemic effect was observed in group A, in which serum bilirubin concentrations were reduced to 1.7±0.45 mg/dl from pretransplantation levels of 6.9±1.2 mg/dl. This effect was even greater than that observed after transplantation of 20 times more hepatocytes without ligation (group E). Specific endonuclease digestion of a polymerase chain reaction-amplified segment of the ugt1 gene from hepatic DNA showed that up to 25% of the DNA was of donor origin. This paralleled the hepatic bilirubin-UDP- glucuronosyltransferase activity, which was above 50% of normal. The results indicate that the transplanted hepatocytes proliferate preferentially within the regenerating lobes, replacing more than 20% of the liver mass with the progeny of the transplanted phenotypically normal hepatocytes.

Original languageEnglish (US)
Pages (from-to)8-13
Number of pages6
JournalTransplantation
Volume64
Issue number1
DOIs
StatePublished - Jul 15 1997

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Portal Vein
Liver Transplantation
Ligation
Hepatocytes
Liver
Transplantation
bilirubin glucuronoside glucuronosyltransferase
Gunn Rats
Injections
Endonucleases
DNA
Bromodeoxyuridine
Jaundice
Bilirubin
Wistar Rats
Regeneration
Digestion
Polymerase Chain Reaction
Control Groups

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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Massive repopulation of rat liver by transplantation of hepatocytes into specific lobes of the liver and ligation of portal vein branches to other lobes. / Ilan, Yaron; Roy Chowdhury, Namita; Prakash, Renu; Jona, Vinod; Attavar, Preeti; Guha, Chandan; Tada, Kouji; Roy-Chowdhury, Jayanta.

In: Transplantation, Vol. 64, No. 1, 15.07.1997, p. 8-13.

Research output: Contribution to journalArticle

Ilan, Yaron ; Roy Chowdhury, Namita ; Prakash, Renu ; Jona, Vinod ; Attavar, Preeti ; Guha, Chandan ; Tada, Kouji ; Roy-Chowdhury, Jayanta. / Massive repopulation of rat liver by transplantation of hepatocytes into specific lobes of the liver and ligation of portal vein branches to other lobes. In: Transplantation. 1997 ; Vol. 64, No. 1. pp. 8-13.
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AB - An important consideration in application of hepatocyte transplantation is whether the number of engrafted hepatocytes is sufficient to achieve the desired effect. Here we have evaluated the proliferative potential of transplanted primary hepatocytes during regeneration of hepatic lobes. Two million hepatocytes isolated from congeneic normal Wistar-RHA rats were injected into the main portal vein of deficient, jaundiced Gunn rats. The right branch of the portal vein was ligated 24 hr before hepatocyte transplantation (group A) or transiently clamped during hepatocyte injection (group B) or 24 hr after hepatocyte injection (group C). In these groups, the three lobes supplied by the right branch of the portal vein rapidly atrophied and disappeared in 4 days, whereas the remaining lobes proliferated, as shown by size increase and 5-bromo-2-deoxy-uridine uptake. Two control groups received 2 million (group D) or 20 million hepatocytes (group E) without ligation. Hepatocyte engraftment occurred in all groups. The greatest hypobilirubinemic effect was observed in group A, in which serum bilirubin concentrations were reduced to 1.7±0.45 mg/dl from pretransplantation levels of 6.9±1.2 mg/dl. This effect was even greater than that observed after transplantation of 20 times more hepatocytes without ligation (group E). Specific endonuclease digestion of a polymerase chain reaction-amplified segment of the ugt1 gene from hepatic DNA showed that up to 25% of the DNA was of donor origin. This paralleled the hepatic bilirubin-UDP- glucuronosyltransferase activity, which was above 50% of normal. The results indicate that the transplanted hepatocytes proliferate preferentially within the regenerating lobes, replacing more than 20% of the liver mass with the progeny of the transplanted phenotypically normal hepatocytes.

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