Long-term engraftment of fresh human myeloma cells in SCID mice

Abstract

Using highly purified myeloma cells from patient bone marrow, we established human-murine myeloma chimeras in severe combined immunodeficiency (SCID) mice and documented secretion of monoclonal human immunoglobulins (Hulgs) in the mice for up to 299 days. Monoclonality of circulating Hulgs was found only when highly purified myeloma cells were injected intraperitoneally. In contrast, injection of unfractionated myeloma marrow led to the development of polyclonal Hulgs in the SCID mice. The criteria for myeloma engraftment included prolonged presence of monoclonal Hulgs in the sera of SCID mice and/or detection of human myeloma cells in their tissues by immunohistochemical examination. Ninety-one percent (10/11) of the fresh purified myeloma specimens engrafted in the SCID mice. Fifty-five percent (6/11) of the patient samples resulted in human B-cell grafts, and 45% (5/11) were identifiable as human myeloma chimeras. Pathologic studies showed that most human plasmacytes were located in the peritoneal cavity but metastatic infiltrates were also found in other organs in 69% of the SCID-human myeloma chimeras. This chimeric model should provide a useful tool for characterization of growth modulation and microenvironmental interactions as well as a means of testing new therapeutic approaches to multiple myeloma.

Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos

“…We also injected MM cells from patient BM samples. About 80% of the injected patient MM samples were engrafted, as determined by FC and Q-PCR, which is similar to the engraftment rates obtained with patient samples in NOD/SCID transplantation ( Feo-Zuppardi et al , 1992 ) and similar to our previous reports on patient leukaemia cells injected in turkey embryos ( Grinberg et al , 2009 ). Although the human-to-mouse xenograft is the most commonly used in-vivo system for studying leukaemia and myeloma, most patient samples do not adequately engraft in immune-deficient mice.…”

Animal Models of Multiple Myeloma and Their Utility in Drug Discovery

“…Several new animal models of MM have been created, either through the injection of purified myeloma cells from MM patient bone marrow aspirates (Feo‐Zuppardi et al, ; Kyoizumi et al, ; Namikawa et al, ; Ashman et al, ; Radl, ; Pilarski et al, ; Huang et al, ) or the implantation of human fetal or rabbit bones into immunodeficient mice followed by injections of purified myeloma cells from MM patient bone marrow aspirates (Yaccoby et al, , Yaccoby and Epstein, ; Yata and Yaccoby, ). These cells were successfully engrafted greater than 50% of the time and eventually led to the appearance of serum paraprotein and, in some cases, extramedullary tumors.…”

BCL‐2 expression by leukaemic blasts in a SCID mouse model of biphenotypic leukaemia associated with the t(4;ll)(q21;q23) translocation

“…The SCID mouse (Bosma et al, 1983) has been used to engraft a variety of haematological malignancies. These include ALL (De Lord et al, 1991;Kamel-Reid et al, 1989), AMI, (Cesano r t a/, 1992; Chelstrom et al, 1994), multiple myeloma (Feo-Zuppardi et al, 1992), Waldenstrom's macroglobulinaemia (Al-Katib et al, 1993), Hodgkin's disease (Kapp rt ul, 1993). CLL (Kobayashi et al, 1992) and Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (Cannon et al, 1990).…”