Figure 5
Figure 5. SD-208 can improve anemia in a murine model of TGF-β1–driven bone marrow failure. Mice transgenic for alb/TGF-β were killed at 8 weeks of age and their bone marrows were stained for histology (hematoxylin and eosin and reticulin stain). Transgenic mice demonstrated dysplastic micromegakaryocytes and patchy fibrosis. (A) Blood counts were analyzed at 3 weeks by Advia (Bayer) counter, and alb/TGF+ transgenic mice were found to be significantly anemic compared with WT controls (n = 4; means ± SEM; Nikon, 40×) (B). alb/TGF+ mice were treated with either SD-208 (30 mg/kg per day) or vehicle (placebo, daily) by gastric lavage for 14 days. Blood counts were done on the 14th day and revealed a significant rise in hematocrit after SD-208 treatment (C). The mice were killed and bone marrow cells were plated in methylcellulose with Epo (for BFU-E colonies) and IL-3, IL-6, and SCF (for CFU-GM colonies). SD-208 treatment led to a significant increase in both erythroid and myeloid colony-forming potential compared with placebo (n = 8; means ± SEM; 2-tailed t test; D).

SD-208 can improve anemia in a murine model of TGF-β1–driven bone marrow failure. Mice transgenic for alb/TGF-β were killed at 8 weeks of age and their bone marrows were stained for histology (hematoxylin and eosin and reticulin stain). Transgenic mice demonstrated dysplastic micromegakaryocytes and patchy fibrosis. (A) Blood counts were analyzed at 3 weeks by Advia (Bayer) counter, and alb/TGF+ transgenic mice were found to be significantly anemic compared with WT controls (n = 4; means ± SEM; Nikon, 40×) (B). alb/TGF+ mice were treated with either SD-208 (30 mg/kg per day) or vehicle (placebo, daily) by gastric lavage for 14 days. Blood counts were done on the 14th day and revealed a significant rise in hematocrit after SD-208 treatment (C). The mice were killed and bone marrow cells were plated in methylcellulose with Epo (for BFU-E colonies) and IL-3, IL-6, and SCF (for CFU-GM colonies). SD-208 treatment led to a significant increase in both erythroid and myeloid colony-forming potential compared with placebo (n = 8; means ± SEM; 2-tailed t test; D).

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