Testing of POL5551-mediated expansion in a disease model. (A) Schematic representation of the BM failure model. Young adult C57BL/6 mice (CD45.2⁺) were treated with 4 weekly IP doses of the alkylating agent BU (10 mg/kg). Control mice received dimethyl sulfoxide (DMSO). Eight weeks after the last BU/DMSO injection, POL5551 infusion (100 mg/kg per day for 2 weeks) was administered to 1 set of mice from each group and the other set was sham-operated. At the end of the treatment (10 weeks after last BU/DMSO injection), (B) CFU-C/LSK and (C) LSK SLAM numbers in BM were measured. Data represent the mean ± SEM of 5 mice per group. (D) BM from mice (CD45.2⁺ as in [A]) treated with DMSO (ctr), BU, or BU + POL5551 was transplanted noncompetitively into CD45.1⁺ or CD45.1/2⁺ hosts (1 × 10⁶ BM cells per recipient). Survival was monitored for the indicated time period (8 recipients per group at experiment start). Forty weeks later, BM composition of the recipients was analyzed. (E) Measured absolute WBC counts in the BM are shown. ***P < .001; **P < .01; *P < .05.