Figure 6.
Transfusion of healthy mouse RBCs reverses SCD mouse phenotype. (A) Macroscopic appearance of spleen from AA mice and SS mice treated with vehicle or transfusion (left panel). One representative image from 6 mice per group is shown. Transfused SS mice were euthanized at 3 weeks (3 w) and 6 weeks (6 w) of treatment. Bar graph showing ratio of spleen weight/mouse weight for AA and SS mice treated with vehicle or transfusion (n = 6; 14-16 weeks old; 3 female mice and 3 male mice) (middle panel). Representative ultrasound images of intact AA and SS spleens followed up during treatment with vehicle or transfusion illustrating the dimension of the spleen (right panels). The solid red lines depict the 3D spleen reconstruction, showing the time-dependent reduction in the spleen in transfused SS mice. Spleen volumes were determined using Vevo software (supplemental Figure 7A). *P < .05 vs AA mice, °P < .05 vs vehicle-treated SS mice, 2-way analysis of variance (ANOVA) with Bonferroni correction for multiple comparisons. (B) Hemoglobin (Hb) and reticulocyte (Retics) counts in SS mice during the 6-week RBC transfusion regimen (n = 6; 10-16 weeks old; 3 female mice and 3 male mice). The red line refers to reticulocytes, and the blue line refers to hemoglobin. °P < .05 vs baseline values, 1-way ANOVA with the Dunnett test for longitudinal comparison. (C) Distribution graphs generated for RBC volume and hemoglobin concentration (RBC HC) of RBCs from AA mice and SS mice treated with vehicle or transfusion (left panels). The single experiment shown is representative of 6 additional experiments with similar results. Related values for cell hemoglobin concentration mean (CHCM) and hemoglobin distribution width (HDW) are shown in the bar graph (right panels). n = 6 (14-16 weeks old; 3 female mice and 3 male mice). *P < .05 vs AA mice, °P < .05 vs vehicle-treated SS mice, 2-way ANOVA with Bonferroni correction for multiple comparisons. (D) Representative reverse-phase HPLC of hemolysates from SS mice transfused with AA RBCs at 1 week (1 w), 3 weeks (3 w), and 6 weeks (6 w) of the transfusion regimen (left panel). Quantitation of HbS and HbA in SS mice treated with vehicle or transfusion at 1, 3, and 6 weeks of RBC transfusion, shown as the percentage of total Hb (right panel; n = 6; 10-16 weeks old; 3 female mice and 3 male mice). Data are mean ± standard error of the mean (SEM). *P < .02 vs baseline values, 1-way ANOVA with the Dunnett test for longitudinal comparison. (E) Frequency of CD44+ Ter119+ FSChi cells in the BM (left panel) and spleen (right panel) from AA mice and SS mice treated with vehicle or transfusion at 3 weeks (3w) and 6 weeks (6w) of RBC transfusion (n = 6; 10-16 weeks old; 3 female mice and 3 male mice). The boxes of the graphs represent the interquartile range (difference between the 25th and 75th percentile) with a middle line for the median. *P < .05 vs AA mice, °P < .02 vs SS mice, 2-way ANOVA with Bonferroni correction for multiple comparisons.

Transfusion of healthy mouse RBCs reverses SCD mouse phenotype. (A) Macroscopic appearance of spleen from AA mice and SS mice treated with vehicle or transfusion (left panel). One representative image from 6 mice per group is shown. Transfused SS mice were euthanized at 3 weeks (3 w) and 6 weeks (6 w) of treatment. Bar graph showing ratio of spleen weight/mouse weight for AA and SS mice treated with vehicle or transfusion (n = 6; 14-16 weeks old; 3 female mice and 3 male mice) (middle panel). Representative ultrasound images of intact AA and SS spleens followed up during treatment with vehicle or transfusion illustrating the dimension of the spleen (right panels). The solid red lines depict the 3D spleen reconstruction, showing the time-dependent reduction in the spleen in transfused SS mice. Spleen volumes were determined using Vevo software (supplemental Figure 7A). *P < .05 vs AA mice, °P < .05 vs vehicle-treated SS mice, 2-way analysis of variance (ANOVA) with Bonferroni correction for multiple comparisons. (B) Hemoglobin (Hb) and reticulocyte (Retics) counts in SS mice during the 6-week RBC transfusion regimen (n = 6; 10-16 weeks old; 3 female mice and 3 male mice). The red line refers to reticulocytes, and the blue line refers to hemoglobin. °P < .05 vs baseline values, 1-way ANOVA with the Dunnett test for longitudinal comparison. (C) Distribution graphs generated for RBC volume and hemoglobin concentration (RBC HC) of RBCs from AA mice and SS mice treated with vehicle or transfusion (left panels). The single experiment shown is representative of 6 additional experiments with similar results. Related values for cell hemoglobin concentration mean (CHCM) and hemoglobin distribution width (HDW) are shown in the bar graph (right panels). n = 6 (14-16 weeks old; 3 female mice and 3 male mice). *P < .05 vs AA mice, °P < .05 vs vehicle-treated SS mice, 2-way ANOVA with Bonferroni correction for multiple comparisons. (D) Representative reverse-phase HPLC of hemolysates from SS mice transfused with AA RBCs at 1 week (1 w), 3 weeks (3 w), and 6 weeks (6 w) of the transfusion regimen (left panel). Quantitation of HbS and HbA in SS mice treated with vehicle or transfusion at 1, 3, and 6 weeks of RBC transfusion, shown as the percentage of total Hb (right panel; n = 6; 10-16 weeks old; 3 female mice and 3 male mice). Data are mean ± standard error of the mean (SEM). *P < .02 vs baseline values, 1-way ANOVA with the Dunnett test for longitudinal comparison. (E) Frequency of CD44+ Ter119+ FSChi cells in the BM (left panel) and spleen (right panel) from AA mice and SS mice treated with vehicle or transfusion at 3 weeks (3w) and 6 weeks (6w) of RBC transfusion (n = 6; 10-16 weeks old; 3 female mice and 3 male mice). The boxes of the graphs represent the interquartile range (difference between the 25th and 75th percentile) with a middle line for the median. *P < .05 vs AA mice, °P < .02 vs SS mice, 2-way ANOVA with Bonferroni correction for multiple comparisons.

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