Human neuroblastoma cell growth in xenogeneic hosts: comparison of T cell-deficient and NK-deficient hosts, and subcutaneous or intravenous injection routes

Turner, William J.; Chatten, Jane; Lampson, Lois A.

doi:10.1007/bf00177834

Cited by 13 publications

(6 citation statements)

References 20 publications

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“…These results demonstrate that an NK cell‐mediated cytotoxic mechanism in SCID/Alb‐uPA mice plays a critical role in the rejection of human hepatocytes. It has been reported that NK activity in vivo and in vitro is less in homo (beige,beige) < hetero (beige,+) < wild type (+,+) [45,46]. Although there is no reliable assay for hetero beige status versus no beige mutation, these results would provide support for the possibility that high hAAT animals from our colony are hetero for the beige mutation as they accept MHC class I knockout marrow and human hepatocytes better than low hAAT animals.…”

Section: Discussionmentioning

confidence: 99%

Critical role of natural killer cells in the rejection of human hepatocytes after xenotransplantation into immunodeficient mice

Kawahara¹,

Douglas²,

Lewis³

et al. 2010

Transplant International

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Summary The severe combined immunodeficiency/albumin linked‐urokinase type plasminogen activator (SCID/Alb‐uPA) human liver chimeric mouse model has added a new dimension to studies of liver based human diseases and has important potential for study of human hepatic drug metabolism. However, it remains unclear if natural killer (NK) cell in SCID/Alb‐uPA mice has an important negative impact on engraftment and expansion of human hepatocytes after transplantation. Here, we explore the role of mouse NK cells in the rejection of transplanted human hepatocytes in SCID/Alb‐uPA mice. We assessed NK cell activity in vivo, using 125I‐iodo‐2′‐deoxyuridine incorporation assay. Low serum human alpha‐1 antitrypsin (hAAT, <10 μg/ml) recipients, representing graft failure, showed resistance to engraftment of MHC class I knockout marrow (indicating high NK cell activity), while NK cell‐depleted low hAAT recipients and high hAAT (>100 μg/ml) recipients accepted MHC class I knockout marrow, indicating a correlation between low NK cell activity, in vivo, and high level human hepatocyte engraftment. We also showed that higher level engraftment of human hepatocytes was achieved in both NK cell‐depleted SCID/Alb‐uPA mice and Rag2−/−γc−/−/Alb‐uPA (T,B and NK cell deficient) mice compared with untreated SCID/Alb‐uPA mice. These results support a critical role for mouse NK cells in the rejection of human hepatocytes xenotransplanted to immunodeficient mice.

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Section: Discussionmentioning

confidence: 99%

Critical role of natural killer cells in the rejection of human hepatocytes after xenotransplantation into immunodeficient mice

Kawahara¹,

Douglas²,

Lewis³

et al. 2010

Transplant International

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“…The multiple potential interactions among MHC' cells, T cells, and adjacent cells make it necessary to evaluate MHC expression and function at the level of the whole tissue. As discussed below, this may not be readily predicted from the behavior of isolated cells in culture (Turner et al, 1990). Ways of defining the in situ MHC expression and of reconciling divergent findings are stressed in this chapter.…”

Section: Relationship Between Mhc Restriction and T Cell Function Andmentioning

confidence: 98%

Interpreting MHC class I expression and class I/class II reciprocity in the CNS: Reconciling divergent findings

Lampson

1995

Microscopy Res & Technique

103

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MHC-restricted T cells are thought to contribute to clinical demyelination in MS and other circumstances. The step-by-step mechanisms involved and ways of controlling them are still being defined. Identification of the MHC+ cells in the CNS in situ has been controversial. This chapter reviews MHC expression in neural tissue, including normal, pathological, experimental, and developing tissue in situ and isolated cells in vitro. A basic pattern is defined, in which MHC expression is limited to nonneural cells and strongest class I and II expression are on different cell types. Variations from the basic pattern are reviewed. Ways of reconciling divergent findings are discussed, including the use of "mock tissue" to help choose between technical and biological bases for divergent findings, the potential contribution of internal antigen to the in situ staining patterns, and the possibility that class I upregulation is actively suppressed in situ. Functional implications of the observed patterns of MHC expression and ways of confirming the function of each MHC+ cell type in situ are described. It is suggested that modulating MHC expression in different cell types at different times or in different directions might be desirable.

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“…With few exceptions, 32 NB xenograft models described so far do not metastasize unless tumor cells are injected intravenously. 33,34 This makes them less useful for therapeutic studies of poor-prognosis metastasizing NB since metastasis models produced by i.v. injection only mimic the later but not the initial stages of the metastatic process.…”

Section: Transplantable Syngeneic Modelsmentioning

confidence: 99%

Murine models for experimental therapy of pediatric solid tumors with poor prognosis

Beltinger

Debatin

2001

Int. J. Cancer

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Novel therapeutic strategies are required for pediatric solid tumors with poor prognosis such as metastasizing neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma. A prerequisite for the development of such new therapies is the availability of murine models. To be useful for therapeutic studies, these models should not only recapitulate the genetic alterations characteristic of the human disease but should also mimic the metastatic process and the response to current therapy, both of which ultimately determine the fate of children with these tumors. This review scrutinizes the utility of existing murine models of neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma for investigating novel therapies. Much experience has been gained with both syngeneic and xenogeneic transplantable models of these tumors, while transgenic and knockout mice are just beginning to be available for therapeutic investigations. Modeling the genetic aberrations characterizing these tumors may provide faithful models for therapeutic studies in the future.Key words: mouse model; neuroblastoma; rhabdomyosarcoma; Ewing's sarcoma; therapy In contrast to adults, most children with localized solid tumors can be cured today. However, subsets of pediatric solid tumors still carry a poor prognosis. Besides brain tumors, which will not be considered in this review because of their unique features, these tumors include metastatic neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma. As a paradigm, the dismal prognosis for advanced-stage neuroblastoma has not changed much for decades. While current therapy is largely based on clinical studies of combined chemo-and radiotherapy, the development of new therapies has to rely on clinically relevant murine models of these tumors. This is especially important in pediatric oncology, given the low number of children eligible for phase I trials. 1 The purpose of this review is to discuss the utility of existing murine models of poor-prognosis extracranial pediatric solid tumors for investigating novel therapies. Available mouse models for neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma are reviewed. These tumors have been selected because of their wellcharacterized genetic alterations amenable to mouse modeling and molecular therapeutic strategies. THE "IDEAL" MURINE MODEL OF A SOLID TUMOR FOR THERAPEUTIC RESEARCHThe general limitations of therapeutic research with both transplantable tumor models (syngeneic and xenogeneic) and "spontanously" arising tumors in transgenic or knockout mice have recently been reviewed. 2,3 The characteristics of an "ideal" murine model of a solid tumor have been well defined, as follows:1. Some tumors, especially tumors of childhood, are well described on the genetic level and show characteristic genetic alterations. These changes should obviously be present in the tumor model if the experimental approach targets these changes. However, if the therapy to be tested does not specifically target the etiologic mutation but the ensuing molecular pathology, mouse models that show...

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Human neuroblastoma cell growth in xenogeneic hosts: comparison of T cell-deficient and NK-deficient hosts, and subcutaneous or intravenous injection routes

Cited by 13 publications

References 20 publications

Critical role of natural killer cells in the rejection of human hepatocytes after xenotransplantation into immunodeficient mice

Critical role of natural killer cells in the rejection of human hepatocytes after xenotransplantation into immunodeficient mice

Interpreting MHC class I expression and class I/class II reciprocity in the CNS: Reconciling divergent findings

Murine models for experimental therapy of pediatric solid tumors with poor prognosis

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