Humanized mice allow engraftment and growth of primary MM cells. (A) Mice were implanted with 4 MSC-loaded BCP scaffolds (#); one control was loaded with MSCs and exposed to 30 Gy of x-rays before implantation (*) and the other control was without MSCs (§). Mice were inoculated with mononuclear cells (MNCs) from patient 3 either directly into the ossicles (left panel) or by intracardiac injection (right panel). Representative images of ossicles inoculated via both injection procedures are shown. (B) Immunohistochemical sections of an ossicle from a humanized mouse inoculated with MNCs of patient 4 stained by HE (left panel) or anti–human CD138 (middle panel), and the femur of the corresponding mouse stained by anti–human CD138 (right panel). Representative pictures are shown. (C) Flow cytometric analysis of the blood and ossicles of humanized mice with anti–human CD138. Representative flow cytometry plots of the blood of mice inoculated with MNCs of patient 1, 3, and 4, and cells retrieved from an ossicle of a mouse inoculated with MNCs of patient 4 are shown. (D) FISH analysis of MNCs of patient 4 and cells retrieved from an ossicle of a mouse inoculated with MNCs of patient 4 for t(4;14)(p16;q32). Shown are 2 representative pictures hybridized with the LSI IGH/FGFR3 probes of metaphase cells of patient 4 (top panel) and corresponding mouse (bottom panel). der(4) indicates derivative chromosome 4; der(14), derivative chromosome 14; mar, marker chromosome; and 4 and 14, normal copies of chromosomes 4 and 14.