Hepatocyte transplantation

Ascher, Nancy L.

doi:10.1002/lt.500010212

Cited by 5 publications

(3 citation statements)

References 25 publications

(5 reference statements)

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“…Only preliminary studies have been performed to address the second area. To date, the majority of published hepatocyte transplant studies have focused on the ability of transplanted hepatocytes to correct inborn errors of metabolism in animals (13)(14)(15)(16)(17) and humans (18) or to rescue liver failure in rats or larger animals (19)(20)(21)(22)(23)(24) and humans (25). Few studies have addressed the immunogenicity of allogeneic hepatocytes in vivo.…”

Section: Introductionmentioning

confidence: 99%

Unusual patterns of alloimmunity evoked by allogeneic liver parenchymal cells

Bumgardner

Orosz

2000

Immunological Reviews

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Despite the widely accepted view of the liver as an immunoprivileged tissue, purified allogeneic liver parenchymal cells delivered to the liver of a recipient mouse are highly antigenic. A functional transgenic model of hepatocyte transplantation in mice is used to explore host immune responses to allogeneic hepatocytes. Transplanted hepatocytes expressing human alpha-1-antitrypsin (hA1AT) are monitored for survival by the secretion of the transgene product hA1AT. Transplantation of transgenic hepatocytes into syngeneic or immunoincompetent severe combined immunodeficiency disease (SCID) mice results in indefinite hepatocellular allograft survival. However, transplantation of transgenic hepatocytes into allogeneic hosts results in rapid hepatocyte rejection. This rejection response is associated with prominent delayed type hypersensitivity responses to cellular alloantigen but minimal donor-reactive humoral immunity. Hepatocyte rejection is not controlled by host treatment with anti-CD4 mAb despite the ability of the same treatment regimen to produce indefinite survival of donor-matched heart allografts. Host immune responses to allogeneic hepatocytes utilize CD40L/CD40 but not CD28/B7 co-stimulation, unlike the activation of both of these systems in responses to other allografts. Furthermore, C57BL/6 mice which have been induced by anti-CD4 mAb or gallium nitrate treatment to accept heart allografts promptly reject donor-matched transgenic hepatocytes. Studies in reconstituted SCID, CD4 knockout (KO), and CD8 KO mice demonstrate that hepatocyte rejection can be initiated independently by either CD4+ T cells or CD8+ T cells, which again diverges from what has been observed for most other types of allografts. This may account for the relative resistance to immunoprotection for hepatocellular allografts with conventional immunosuppressive agents and to immunoregulatory states induced by other allografts. Three models of hepatocyte rejection are discussed.

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Section: Introductionmentioning

confidence: 99%

Unusual patterns of alloimmunity evoked by allogeneic liver parenchymal cells

Bumgardner

Orosz

2000

Immunological Reviews

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“…Recipients (group R) underwent a two-thirds hepatectomy by the removal of the central and the right lateral lobes, as originally described by Higgins and Anderson (16). Partial hepatectomy is used in many models of HT as an exogenous factor to enhance hepatocyte division in the recipient liver (17). All the surgeries were performed between 10 a.m. and 2 p.m. in order to avoid alterations due to circadian rhythm.…”

Section: Partial Hepatectomy Of Recipientsmentioning

confidence: 99%

First approaches for the transplantation of hepatocytes from Wistar rat preneoplastic livers into healthy recipients

Vera¹,

Biancardi²,

Bottai³

et al. 2019

Rev Esp Enferm Dig

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Background: the shortage of donors of hepatocyte transplantation therapy led to the use of so-called marginal donors. Some donors may have a hepatic illnesses that is associated with hepatic preneoplasia with foci of altered hepatocytes (FAH). Aims: to determine whether recipients developed FAH upon transplantation with hepatocytes from a preneoplastic liver and whether FAH progresses to a preneoplastic hepatocyte-derived tumor (PHDT), up to 60 days after transplantation. Material and methods: male Wistar adult rats were used as donors and recipients. Donors underwent a 2-phase model of liver preneoplasia for hepatocyte isolation. Recipients underwent a partial two thirds hepatectomy and received 150,000 hepatocytes. Recipients were euthanized seven and 60 days after transplantation. The number of FAH per liver area, percentage of liver occupied by FAH, the hepatic enzymatic profile, the percentage of prothrombin time (PT), the proliferative index (PI) and liver morphology were analyzed. Results: recipients developed few and very isolated FAH. No statistical differences were found between hepatic enzyme activities and PT. There were no differences between the groups with regard to the number of FAH per liver area and percentage of liver occupied by FAH after 60 days. The PI decreased on day 60 compared to day seven. No morphological alterations were found. Conclusions: recipients developed few FAH that did not increase in number or size, nor did they progress to PHDT and had normal plasma biochemical features and liver morphology up to 60 days post-transplant. Additional studies are needed to determine whether FAH development constitutes a risk for recipients while waiting for whole organ transplant.

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“…In to a definitive immunosuppression. Experimental studies and recent clinical applications suggested hepatocyte fact, little is known about the immunogenicity of isolated hepatocytes, allogeneic hepatocyte rejection, and transplantation as an alternative to liver transplantation in the treatment of some hepatic failure and liver-based the ways to prevent it (3). Recent studies suggested that allogeneic hepatocyte rejection may follow some un-metabolic diseases, with the further advantage to obviate the need for a long surgical intervention with its associ-usual pathways and therefore may need specific immunosuppressive strategies (10).…”

Section: Introductionmentioning

confidence: 99%

Comparative Phenotype and Immunogenicity of Freshly Isolated and Immortalized Rat Hepatocytes

Kaulek

Sass

Alexandre³

et al. 2001

Cell Transplant

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Immortalized hepatocytes are an attractive cell source for hepatocyte transplantation and gene transfer. We compared the phenotype and immunogenicity of freshly isolated (FIH) and immortalized (IMH) rat hepatocytes. Effect of culture and proinflammatory cytokines (TNF-α, IFN-γ) was studied on phenotype. FIH were isolated by collagenase digestion. Two SV40 immortalized hepatocyte cell lines were tested (RH1 and P9). Immunophenotyping was performed by FACS analysis using anti-rat-specific antibodies. Immunogenicity was evaluated by a mixed lymphocyte hepatocyte reaction (MLHR). FIH suspension was an almost homogeneous parenchymal cell population with few (1-2%) CD8 + cells. FIH showed a positive staining for ICAM-1 (20-35%) and for Class I (RT1A, 30-60%) but no staining for Class II (RT1B). After 48 h of culture, the already ICAM-1-positive cells were more strongly stained and additionally 3.6% of the cells (possibly endothelial cells) were Class II positive. IMH showed a consistent expression of Class I (93-97%) and ICAM-1 (95-97%) but no expression of Class II. Culture of IMH for 48 h had no effect on Class II expression but increased ICAM-1 expression. Addition of TNF-α at 1000 UI/ml to cultures of FIH or IMH increased Class I and ICAM-1 expression whereas IFN-γ (50 or 1000 UI/ml) had no evident effect. Hepatocyte immunogenicity, assessed in MLHR and appreciated by the stimulation index (SI) test/SI syngeneic control, was similar for IMH (RH1: 2.68 ± 0.89; P9: 2.37 ± 0.78) and FIH (2.52 ± 0.18). In conclusion, despite some quantitative immunophenotypic differences, FIH and IMH induced the same proliferation rate of allogeneic T lymphocytes. Thus, immortalized hepatocytes may constitute an appropriate cellular model to study the prevention of hepatocyte rejection by gene transfer. 739 740 KAULEK ET AL.

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Hepatocyte transplantation

Cited by 5 publications

References 25 publications

Unusual patterns of alloimmunity evoked by allogeneic liver parenchymal cells

Unusual patterns of alloimmunity evoked by allogeneic liver parenchymal cells

First approaches for the transplantation of hepatocytes from Wistar rat preneoplastic livers into healthy recipients

Comparative Phenotype and Immunogenicity of Freshly Isolated and Immortalized Rat Hepatocytes

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