Fig. 4

BMSCs reduce hepatocyte apoptosis and promote proliferation via induction of HO-1 in the setting of ALF. a TUNEL (marking apoptosis) and Ki67 (a proliferation marker) in livers 72 h after D-Gal/LPS (magnification × 200). b Numbers of TUNEL- + and Ki67- + cells in each group (n = 6 per group). ALF livers had the highest number of TUNEL- + cells. BMSCs significantly reduced numbers of TUNEL- + cells (p < 0.05); Znpp blunted the anti-apoptotic effect of BMSCs (p < 0.05). BMSC and hemin also resulted in significantly less TUNEL- + cells vs. ALF (p < 0.05). BMSCs significantly increased the number of ki67- + cells relative to ALF livers (p < 0.05); Znpp blunted the BMSC effect on proliferation (p < 0.05). BMSC plus hemin also increased the number of ki67-positive cells vs. ALF livers (p < 0.05). c Western blot of Bcl-2 and Bax protein levels (normalized to β-actin standard). d The Bcl-2/Bax ratio decreased significantly in ALF livers. BMSCs infusion increased the Bcl-2/Bax ratio (p < 0.05); Znpp blunted this effect of BMSCs (p < 0.05). BMSCs plus hemin treatment also increased Bcl-2/Bax ratios vs. ALF livers (p < 0.05). Treatment groups: control, ALF, ALF followed by intravenous MSCs (ALF + MSC) 1 h post-induction, ALF followed by MSCs and Znpp (ALF + MSC + Znpp) 1 h post-induction, and ALF followed by hemin (ALF + hemin) 1 h post-induction. Data are mean ± SD. (^* p < 0.05 vs. control group; ^$ p < 0.05 vs. ALF group; ^# p < 0.05 vs. ALF + MSC group). Abbreviations: ALF acute liver failure, BMSCs bone marrow-derived mesenchymal stem cells, D-Gal d-Galactosamine HO-1 heme oxygenase-1, LPS lipopolysaccharide, TUNEL 2’-deoxyuridine 5’-triphosphatenick-end labeling, Znpp zinc protoporphyrin