Protection and expansion of BDSCs mitigated biliary dysfunction in hepatic GVHD. (A-J) Lethally irradiated BDF1 mice were transplanted as in Figure 1A. Allogeneic (Allo) recipients were intraperitoneally (i.p.) injected with 5 mg/kg SB-431542 daily from day 14 to day 28 after allogeneic HCT. (A) A schematic overview of SB-431542 treatment. Representative images (B) and numbers (C) of organoids derived from the right lobe of the livers on day 28 after HCT (n = 8-10/group). Bar, 500 μm. (D) The proportion of cleaved caspase 3 (cCaspase3)⁺ BECs on day 21 (n = 7-8/group). (E) Relative expression of Mmp7 in the liver on day 28 (n = 13-15/group). (F) Plasma levels of total bilirubin on day 28 (n = 12-13/group). Representative hematoxylin and eosin images of the liver (G), pathologic liver GVHD scores (H; n = 15/group), bile duct pathologic scores (I: n = 15/group), and pathologic intestinal GVHD scores (J; n = 15/group) on day 28. Bar, 100 μm. (K-N) Lethally irradiated B6 recipients were transplanted from BALB/c donors, and i.p. injected with SB-431542 daily from day 14 to day 28 after HCT. Representative images (K) and numbers (L) of organoids derived from the right lobe of the liver on day 28 (n = 10/group), the proportion of cCaspase3⁺ BECs on day 21 (M; n = 10/group), and pathologic liver GVHD scores on day 28 (N; n = 10/group). Bar, 500 μm. Data from 2 (C-F, L-N) or 3 (H-J) independent experiments were combined and shown as mean ± standard error. ∗P < .05, ∗∗P < .01, ∗∗∗P < .005.