Donor HSPCs engraftments recapitulate disease pathophysiology. (A) Flow cytometry analyses show multilineage differentiation within organoids of CellVue-labeled donor HSPCs. Each organoid was engrafted with 5 × 10³ CD34⁺ HSPCs derived from a normal bone marrow sample. Ten organoids were pooled for each assay. The patient’s primary bone marrow sample was analyzed, as shown on the right panels, to confirm that the CD34⁺ cells do not coexpress lineage markers. The percentages of the indicated populations are presented. (B) 3D imaging reveals HSPCs from the bone marrow samples of a patient with MDS engraft within the vascular niches of the organoids. (C) Same as panel A, except that CD34⁺ HSPCs derived from 3 different patients with MDS were engrafted separately. (D) Statistical analysis of CellVue⁺ engraftments, with each point representing an independent flow cytometry assay using CD34⁺ HSPCs from a distinct patient sample. Ten organoids were pooled for each assay. n = 3 in each group. Student t test, ∗P < .05; ∗∗P < .01.