Treatment of hypercholesterolemia in the Watanabe rabbit using allogeneic hepatocellular transplantation under a regeneration stimulus.

Abstract:

:Numerous studies have reported successful allotransplantation of hepatocytes. However, none have shown long-term correction of a liver-related metabolic defect. In this study, we used a method of regional hepatocyte transplantation and subsequent induction of transplanted cell proliferation by regeneration response in the transplant-bearing liver lobes. New Zealand White rabbits were used as cell donors and Watanabe heritable hyperlipidemic (WHHL) rabbits were used as cell recipients (2 x 10(8) cells/rabbit). All recipient rabbits were maintained on daily cyclosporine. Two weeks after baseline serum cholesterol determination, group I WHHL rabbits (n = 7) received an infusion of cells into the right lateral liver lobe, and a loose ligature was placed around the portal venous branch supplying the anterior lobe. After 1 week, to allow engraftment, the portal venous branch was ligated, which resulted in the atrophy of the affected liver parenchyma and induction of hyperplasia in the transplant-bearing liver tissue. Group II rabbits (n = 6) were transplanted with New Zealand White hepatocytes without portal branch ligation (PBL) and group III rabbits (n = 4) were subjected to sham transplantation (saline) and PBL. The experimental period extended to 150 days after transplantation. All WHHL rabbits transplanted with normal hepatocytes showed reduction in serum cholesterol and low-density lipoprotein (LDL) levels. Group I (PBL-stimulated) recipients demonstrated a more pronounced and sustained effect than group II animals (P < 0.05). Group III controls showed only a slight, typical for aging decrease in serum cholesterol. Group I recipient livers perfused with LDL labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI) showed much higher numbers of DiI-LDL-positive hepatocytes than those of group II recipients. In conclusion, a liver regeneration stimulus enhanced the population of transplanted hepatocytes and their functional effect in a large animal model of inborn error of liver metabolism.

journal_name

Transplantation

journal_title

Transplantation

authors

Eguchi S,Rozga J,Lebow LT,Chen SC,Wang CC,Rosenthal R,Fogli L,Hewitt WR,Middleton Y,Demetriou AA

doi

10.1097/00007890-199609150-00008

subject

Has Abstract

pub_date

1996-09-15 00:00:00

pages

588-93

issue

5

eissn

0041-1337

issn

1534-6080

journal_volume

62

pub_type

杂志文章
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  • Effect of preprocurement ventilation on lungs donated after cardiac death in a canine lung transplantation model.

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    更新日期:1992-10-01 00:00:00

  • Higher frequency of high-grade rejections in cardiac allograft patients after Quilty B lesions or grade 2/4 rejections.

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    pub_type: 杂志文章

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    authors: Smith RN,Chang Y,Houser S,Dec GW,Grazette L

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    journal_title:Transplantation

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    doi:

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    pub_type: 杂志文章

    doi:10.1097/00007890-198908000-00017

    authors: Crawford SW,Hackman RC,Clark JG

    更新日期:1989-08-01 00:00:00

  • Selective inhibition of vascular cell adhesion molecule-1 expression by verapamil in human vascular endothelial cells.

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    pub_type: 杂志文章

    doi:10.1097/00007890-199703150-00024

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    更新日期:1997-03-15 00:00:00

  • Urolithiasis after kidney transplantation in pediatric recipients: a single center report.

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    doi:10.1097/01.tp.0000139543.56886.de

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  • Long-term outcome of simultaneous kidney-pancreas transplantation: analysis of 61 patients with more than 5 years follow-up.

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    pub_type: 杂志文章

    doi:10.1097/00007890-198111000-00018

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    更新日期:1987-08-01 00:00:00