Figure 7 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies

<p>Bone marrow organoids support the engraftment, survival, and proliferation of cells from patients with myeloid and lymphoid hematologic malignancies. <b>A,</b> Organoids engrafted with CellVue-labeled model infant ALL cells from xenografts (Xeno iALL), primary cells from a patient with untreated CML, and THP-1 cells, an acute myeloid leukemia cell line. CellVue⁺ cells are visible throughout the volume of organoids. <b>B,</b> Organoids seeded with CD138⁺ cells isolated from bone marrow aspirates of patients with multiple myeloma show CellVue⁺ CD38⁺ plasma cell engraftment. <b>C–E,</b> Viability and proliferation of cells from 4 donors with multiple myeloma, 6 donors with ALL, and 3 Xeno iALL samples seeded simultaneously in the organoids, a 3D coculture with primary human BM-MSC (3D BM-MSC), and where possible, liquid culture. <b>E,</b> Serial dilution of CellTrace label, indicating cell proliferation, for multiple myeloma, Xeno iALL, and ALL cells in 3D BM-MSC and organoids on days 2, 5, 7, and 12 following thawing and plating. <b>F,</b> Engrafted multiple myeloma cells retained their immunophenotype at day 12 with more consistent maintenance of CD319 and CD38 in organoids than 3D BM-MSC. Representative images are shown. *, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; ns, not significant. <i>n</i> = 4 for multiple myeloma, <i>n</i> = 3 for Xeno iALL, and <i>n</i> = 3 for ALL, with each repeat comprised of a separate donor two-way ANOVA with repeated measures and multiple comparisons (organoid cultures vs. 3D BM-MSC; Fisher least significant difference) for ALL and multiple myeloma and multiple unpaired <i>t</i> test for Xeno iALL data. BM, bone marrow; FSC, forward scatter.</p>