Long-term human hematopoiesis in SCID-hu mice bearing transplanted fragments of adult bone and bone marrow cells.

Modelling human leukemia and lymphoma in severe combined immunodeficient (SCID) mice: practical applications.

We have evaluated the severe combined immunodeficient (SCID) mouse as an in-vivo model for the study of non-Hodgkin's lymphomas (NHL). Characterization of the immune system of the animals in our SCID mouse colony was carried out to assess the numbers of lymphoid cells present, to determine natural killer (NK) cell activity as a function of age and to examine the histology of the lymphoid organs. In this study four human NHL established cell lines (Daudi, Namalwa, U937, MC116), lymphoma cells from four fresh NHL biopsies and normal peripheral blood mononuclear cells (PBMC) and bone marrow cells were investigated, after intraperitoneal injection into the mice. The presence of the human NHL cells in the peritoneum and spleen was assessed by FACS analysis. The colonization potential was investigated in a range of tissues by polymerase chain reaction (PCR) amplification of human repetitive sequences. These studies revealed clear differences in the abilities of the NHL cell types to colonize the SCID mice. Namalwa, Daudi and U937 cells demonstrated the highest efficiency of colonization and readily formed tumours, whereas MC116, the NHL biopsy cell populations and the non-malignant lymphoid cells showed little ability to survive and colonize other tissues in the SCID mice. Whole body irradiation of the SCID mice appeared to improve the survival of human PBMC, NHL biopsy cells and MC116 cells in the peritoneum, but had little effect on their colonization potential. The significance of these studies is discussed.

Analysis of the Colonization of Unirradiated and Irradiated SCID Mice by Human Lymphoma and Non-malignant Lymphoid Cells

Normal and Benign Reactive Hematopoietic Tissues

Severe combined immunodeficient (SCID) mice were transplanted with biopsy material from 18 cases of Hodgkin’s disease (HD) and 23 biopsies from non-Hodgkin’s lymphoma. Five of the HD (3 lymphocyte predominant, 1 nodular sclerosing and 1 mixed cellularity) and 7 of the non-Hodgkin’s lymphomas (3 centroblastic, 1 immunoblastic, 1 follicular lymphoma and 2 biopsies from a case of large cell anaplastic lymphoma) produced tumours in mice. All the SCID HD-derived tumours had a B-cell phenotype and expressed the Epstein-Barr virus (EBV) gene products, EBER RNA, EBNA-2 and LMP-1. Morphologically these tumours resembled polymorphous immunoblastic lymphomas. The EBV-positive tumours all expressed CD23 and CD43. All HD-derived SCID tumours showed clonal immunoglobulin heavy chain rearrangements. One tumour derived from a follicular lymphoma showed similar morphology and phenotype and an identical pattern of EBV gene expression to the HD-derived tumours. Three centroblastic and one immunoblastic lymphoma derived tumours were EBV-negative. These showed a near identical B-cell phenotype to original biopsies and showed identical immunoglobulin gene rearrangements to the original tumours. Tumours derived from the large cell anaplastic lymphoma showed two types of lymphoproliferation in SCID mice; first immunoblastic tumours expressing EBER RNA, EBNA-2 and LMP-1, with immunoglobulin gene rearrangements differing from those of the original tumour; secondly large cell anaplastic tumours showing EBER RNA with little or no LMP-1 or EBNA-2 expression, and immunoglobulin gene rearrangements identical to those of the original tumour.

A SCID Mouse Model of Hodgkin’s Disease? Transplantation of Hodgkin’s and Non-Hodgkin’s Lymphomas Into Severe Combined Immunodeficient Mice

Two EBV-negative human lymphoma cell lines raised in this laboratory and peripheral blood cells of a patient with large cell lymphoma in leukemic phase were injected intravenously or intraperitoneally into C.B.17 SCID mice. One line (OCI-LY18) was derived from the pleural fluid of a patient with a large cell, immunoblastic malignant lymphoma. Cells of this line are of B cell origin and characterized by multiple rearrangements of the JH locus. The second line (OCI-LY17) was grown from the peripheral blood of a patient with a large cell lymphoma of T-cell phenotype which has characteristic rearrangement of the T-cell receptor beta chain. The cells directly obtained from a patient with large cell non-cleaved malignant lymphoma were of B-cell origin. Animals carrying OCI-LY18 developed large tumor masses within 6-8 weeks of inoculation. The tumors were detected in the intestine, mesentery, retroperitoneum, lymph nodes, spleen, lung and kidney. The masses resembled the primary tumor with respect to histological appearance and immunological phenotype. It was possible to generate secondary cell lines from the tumors found in the inoculated SCID mice. Injection of one of these secondary cell lines into SCID mice resulted in the rapid development of lymphoma and as few as 10 cells were sufficient to establish the disease in the inoculated animals. In contrast cells of OCI-LY17 produced small tumor aggregates that did not appear to progress over time and did not cause death of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth of human lymphoma cells in SCID mice.

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Growth of human lymphoma cells in SCID mice.