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Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model

Elswefy, Sahar E; Rashed, Laila A; Younis, Nahla N; Shaheen, Mohamed A; Ghanim, Amal MH

Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM-MSCs) induce liver regeneration of fibrotic liver in rats . Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM-MSCs (3 × 106 cells / rat , once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and α-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P < 0.001), increases in HGF and MMP-2 mRNA and downregulating CK-19 mRNA. Sliymarin, however, induced similar but less prominent effects compared to BM-MSCs. In conclusion, liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA. PMID:26811102

Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model.

Mohamed, Hoda E; Elswefy, Sahar E; Rashed, Laila A; Younis, Nahla N; Shaheen, Mohamed A; Ghanim, Amal M H

2016-03-01

Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM-MSCs) induce liver regeneration of fibrotic liver in rats . Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM-MSCs (3 × 10(6) cells / rat , once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and α-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P < 0.001), increases in HGF and MMP-2 mRNA and downregulating CK-19 mRNA. Sliymarin, however, induced similar but less prominent effects compared to BM-MSCs. In conclusion, liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA. © 2016 by the Society for Experimental Biology and Medicine.

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Relief shown by hachures and form lines. Shows householders' names. In upper left sheet corner: Transf'd from Office of Chf. Engr. Defenses of Washington, to Engr. Dept.--1866. India ink and violet wash. Fold-lined and torn. In left upper margin: 211, L. Sheet 18. LC Civil War maps (2nd ed.) 691.4 Available also through the Library of Congress Web site as a raster image. Vault...
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A general particular plan of the island of Castle William near Boston, shewing the works in their original present state, together with sections thro' the same. Carried on and survey'd ... Scale 1:600; 50 ft. to an in. Manuscript, pen-and-ink and watercolor. Has watermarks. Relief shown by shading. Oriented with north toward the upper right. Imperfect: Hole in center. "No. 11." Includes index to points of interest, inset of "A general plan of the island of Castle William shewing its situation with respect to the adjacent islands," 1:6,000, and two cross section views. LC Maps...
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Scale 1:42,240. LC Civil War Maps (2nd ed.), 525b.2 In this issue, the map is printed on a yellow background with the James and Appomattox rivers colored blue. Map indicates roads, railroads, towns, drainage, vegetation, relief by hachures, houses, and names of residents. Union and Confederate entrenchments are colored blue and red respectively. Description derived from published bibliography. Available also through the Library of...
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