Nonirradiated NOD/SCID-human chimeric animal model for primary human multiple myeloma: a potential in vivo culture system.

The NOD/SCID human chimeric animal model was generated by implanting of human fetal bones (FBs) into subcutaneous sites of NOD/SCID mice (NOD/SCID-hu(+)), followed by inoculation of primary bone marrow mononuclear cells (BMNCs) obtained from patients with multiple myeloma (MM) into the FBs. The BMNCs from 30 patients with MM were inoculated, and 28 (93%) of them revealed evidence of tumor growth of myeloma cells (MCs) in the NOD/SCID-hu(+) mice. Intriguingly, 17 (61%) of the 28 patients' BMNCs inoculated developed not only myeloma in the bone marrow of the FBs, but also extramedullary macrotumors (EMTs) along the periosteum of the FBs. The tumor cells in these EMTs had plasmacytoid morphology and preserved antigens and cytogenetics similar, if not identical, to those in the parent MCs. Moreover, small tumor blocks from nine EMTs were transplanted into subcutaneous sites of subsequent recipient NOD/SCID mice without human FBs (NOD/SCID-hu(-)), and all but one grew successfully. Two of the EMTs have been maintained in the animal model for more than 12 months. The NOD/SCID-hu(+) chimeric animal model is highly efficient for growth of primary MCs and presents clinical features of human MM. The engrafted MCs can be maintained subsequently in NOD/SCID-hu(-) mice as in vivo culture.