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. 2022 Nov 9;13(2):364–385. doi: 10.1158/2159-8290.CD-22-0199

Figure 7.

Figure 7. Bone marrow organoids support the engraftment, survival, and proliferation of cells from patients with myeloid and lymphoid hematologic malignancies. A, Organoids engrafted with CellVue-labeled model infant ALL cells from xenografts (Xeno iALL), primary cells from a patient with untreated chronic myeloid leukemia (CML) and THP-1 cells, an acute myeloid leukemia cell line. CellVue+ cells are visible throughout the volume of organoids. B, Organoids seeded with CD138+ cells isolated from bone marrow aspirates of patients with multiple myeloma show CellVue+ CD38+ plasma cell engraftment. C–E, Viability and proliferation of cells from 4 donors with multiple myeloma, 6 donors with acute lymphoblastic leukemia (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. E, 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. F, 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. *, P < 0.01; **, P < 0.05; ***, P < 0.001. n = 4 for multiple myeloma, n = 3 for Xeno iALL and n = 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 LSD) for ALL and multiple myeloma, multiple un-paired t test for Xeno iALL data.

Bone marrow organoids support the engraftment, survival, and proliferation of cells from patients with myeloid and lymphoid hematologic malignancies. A, 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, Organoids seeded with CD138+ cells isolated from bone marrow aspirates of patients with multiple myeloma show CellVue+ CD38+ plasma cell engraftment. C–E, 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. E, 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. F, 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. *, P < 0.01; ***, P < 0.001; ns, not significant. n = 4 for multiple myeloma, n = 3 for Xeno iALL, and n = 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 t test for Xeno iALL data. BM, bone marrow; FSC, forward scatter.